As one of the leading components in the immune system, neutrophils in the tumor microenvironment (TME) have received considerable attention in recent years. The tumor-killing effects of neutrophils in a variety of tumors have been reported. However, the functions of neutrophils in tumors remain to be completely elucidated, and both anti-tumor and tumor-promotion activities have been reported. This review focuses on the characteristics of neutrophils and their mechanisms of action in the TME, with an emphasis on their anti-tumor activity, including reactive oxygen species (ROS)-induced tumor killing, cytotoxic T lymphocytes (CTLs)-induced tumor killing, trogocytosis, cytotoxic enzymes, and trained immunity. Furthermore, the possible targets and methods of tumor treatment regimens for neutrophils are explored, with the aim of exploring the use of neutrophils in the future as a potential anti-tumor treatment strategy.

Emerging evidence indicates the importance of tertiary lymphoid structures (TLSs) in predicting the outcomes of nonsmall cell lung cancer (NSCLC) patients; however, their prognostic value and correlations with peripheral inflammatory prognostic indices in stage I patients have been less well studied.

Stage I NSCLC patients were recruited retrospectively; the presence and location of TLSs (peritumoral [pTLSs] and intratumoral [iTLSs]) were determined via hematoxylin and eosin (H&E)-stained slides. Peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI), were obtained and compared among these subgroups. Disease-free survival (DFS) and overall survival (OS) were tested via Kaplan-Meier analysis, and risk factors for survival were determined via a Cox proportional hazards model.

A total of 24.73% and 92.73% of patients were positive for pTLSs and iTLSs, respectively. The absolute number of iTLSs was significantly greater than that of pTLSs (P < .001). Low preoperative LMR and ALI were detected only in patients with pTLSs but not in those without. Only pTLS was found to be a risk factor for both DFS and OS, and it was independently associated with OS (HR = 3.93, 95% confidence interval [CI] = 1.16-13.37; P = .028). Accordingly, patients with pTLSs had relatively poor DFS (log rank = 5.46, P = .019) and OS (log rank = 10.48, P = .001) rates.

Among the heterogeneous results concerning the prognostic value of pTLSs and iTLSs in stage I NSCLC, our results for the first time indicated that the presence of pTLSs may predict poor outcomes in these patients and no correlation of iTLSs with the outcomes was validated; however, additional studies with large sample size are needed in future.

The therapeutic approach for metastatic malignant pleural effusion depends on the patient's life expectancy. Can survival be accurately estimated in these patients using a risk-prediction model?

A prospective, single-center study was conducted to examine the prognostic value of pre-established variables (multivariate Cox model). Subsequently, a prognostic score was developed and validated. The inclusion period was 11 years long. Follow-up was conducted until death or for a minimum of 12 months.

The derivation and validation cohorts included 475 and 205 patients, respectively. The prognostic score GASENT (Galicia, Age, Sex, ECOG-PS, Neutrophil/lymphocyte ratio, and Tumor type) was derived from the multivariate analysis of survival. Categorization of patients in the derivation cohort into low-, moderate-, or high-risk yielded median survival times of 477 days (377-665; n=159), 108 days (83-156; n=158), and 35 days (27-47; n=158), respectively. Survival rates at 1, 3, and 6 months were 92%, 83%, and 72%, respectively, for the low-risk group; 80%, 55%, and 36%, respectively, for the moderate-risk group; and 55%, 23%, and 13%, respectively, for the high-risk group. The analysis of areas under the curve revealed that the GASENT model was superior to the LENT score as a survival predictive model at 1 (0.777 vs. 0.737; p=0.009), 3 (0.810 vs. 0.778; p=0.009), and 6 months (0.812 vs. 0.780; p=0.007).

The GASENT predictive model estimates survival in patients with metastatic malignant effusions with significantly greater accuracy than the scores categorizing patients by risk groups.

Sialylation, a key post-translational modification essential for protein function, is regulated by steroid hormones, along with other glycosylations like fucosylation. These modifications influence tumor growth and metastasis by modulating immune activation. MicroRNAs (miRNAs), crucial in gene expression, affect sialylation and are emerging as promising biomarkers in breast cancer, though their prognostic value remains unclear. Sialylation-related miRNAs were identified through Pearson correlation analysis, and an eight-miRNA risk signature was developed using univariate and Least Absolute Shrinkage and Selection Operator (LASSO) regression in the TCGA dataset. The prognostic value was validated in two independent GEO datasets. Multivariate analysis confirmed that the miRNA risk score is an independent predictor of overall survival (OS). A nomogram integrating clinical characteristics and the risk score was created to predict 1-, 3-, and 5-year OS, assessed through calibration curves, ROC curves, and area under the ROC curve (AUC). Biological pathways were explored using GSEA and GSVA, while immune infiltrates were identified through CIBERSORT and TIMER. The eight-miRNA signature effectively predicted OS, recurrence-free survival, and disease-free survival. High-risk patients exhibited increased macrophage and neutrophil levels, indicative of a poor prognosis. High-risk patients, especially those with triple-negative breast cancer, had significantly worse outcomes. This risk score could inform personalized treatment strategies in breast cancer management.

Inflammatory biomarkers have shown prognostic value in Non-Small Cell Lung Cancer (NSCLC), but the inclusion of Adenocarcinoma In Situ (AIS) cases in previous studies may introduce bias. This study aims to evaluate the prognostic significance of inflammatory biomarkers in NSCLC while excluding AIS.

This study included patients who received surgery for lung carcinoma from August 2016 and August 2019. We collected demographic, clinical, laboratory, and outcome information. Inflammatory biomarkers were analyzed using receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox regression to assess their prognostic value.

Higher levels of inflammatory biomarkers correlated with poorer survival, with significant differences in overall survival (OS) between high- and low-expression groups. However, multivariate Cox regression identified age, tumor stage, and differentiation as independent prognostic factors, while biomarkers were not independently predictive.

Inflammatory biomarkers have short-term prognostic value in invasive NSCLC, but traditional clinical and pathological factors remain key for long-term outcomes.

Tumor-associated neutrophils (TANs) play crucial roles in tumor progression, immune response modulation, and the therapeutic outcomes. Despite significant advancements in TAN research, a comprehensive bibliometric analysis that objectively presents the current status and trends in this field is lacking. This study aims to fill this gap by visually analyzing global trends in TANs research using bibliometric and knowledge mapping techniques.

We retrieved articles and reviews related to TANs from the Web of Science core collection database, spanning the period from 2012 to2024. The data was analyzed using bibliometric tools such as Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio) to identify key trends, influential countries and institutions, collaborative networks. and citation patterns.

A total of 6l5 publications were included in the bibliometric analysis, showing a significant upward trend in TANs research over the last two decades. The United States and China emerged as the leading contributors with the highest number of publications and citations. The journal with the most publications in this field is Frontiers in Immunology, Prominent authors such as Fridlender ZG was identified as the key contributor, with his works frequently cited. The analysis highlighted major research themes. including the role of TANs in tumor microenvironment modulation, their dual functions in tumor promotion and suppression, and the exploration of TANs-targeted therapies, Emerging research hotspots include studies on TANs plasticity and their interactions with other immune cells.

This study is the first to employ bibliometric methods to visualize trends and frontiers in TANs research. The findings provide valuable insights into the evolution of the field, highlighting critical areas for future investigation and potential collaborative opportunities. This comprehensive analysis serves as a crucial resource for researchers and practitioners aiming to advance TAN research and its application in cancer therapy.

Neutrophils play a crucial role in the innate immune response as a first line of defense in many diseases, including cancer. Tumor-associated neutrophils (TANs) can either promote or inhibit tumor growth in various steps of cancer progression via mutual interactions with cancer cells in a complex tumor microenvironment (TME). In this study, we developed and analyzed mathematical models to investigate the role of natural killer cells (NK cells) and the dynamic transition between N1 and N2 TAN phenotypes in killing cancer cells through key signaling networks and how adjuvant therapy with radiation can be used in combination to increase anti-tumor efficacy. We examined the complex immune-tumor dynamics among N1/N2 TANs, NK cells, and tumor cells, communicating through key extracellular mediators (Transforming growth factor (TGF-$ \beta $), Interferon gamma (IFN-$ \gamma $)) and intracellular regulation in the apoptosis signaling network. We developed several tumor prevention strategies to eradicate tumors, including combination (IFN-$ \gamma $, exogenous NK, TGF-$ \beta $ inhibitor) therapy and optimally-controlled ionizing radiation in a complex TME. Using this model, we investigated the fundamental mechanism of radiation-induced changes in the TME and the impact of internal and external immune composition on the tumor cell fate and their response to different treatment schedules.

The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China, with the disease's intricate and varied characteristics further amplifying its health impact. Precise forecasting of overall survival (OS) is of paramount importance for the clinical management of individuals afflicted with this malignancy.

To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma.

Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020. Least absolute shrinkage and selection operator, univariate, and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram model was developed to predict gastric cancer patient outcomes. The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves. To evaluate the clinical utility of the model, Kaplan-Meier and decision curve analyses were performed.

A total of ten independent prognostic factors were identified, including body mass index, tumor-node-metastasis (TNM) stage, radiation, chemotherapy, surgery, albumin, globulin, neutrophil count, lactate dehydrogenase, and platelet-to-lymphocyte ratio. The area under the curve (AUC) values for the 1-, 3-, and 5-year survival prediction in the training set were 0.843, 0.850, and 0.821, respectively. The AUC values were 0.864, 0.820, and 0.786 for the 1-, 3-, and 5-year survival prediction in the validation set, respectively. The model exhibited strong discriminative ability, with both the time AUC and time C-index exceeding 0.75. Compared with TNM staging, the model demonstrated superior clinical utility. Ultimately, a nomogram was developed via a web-based interface.

This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients, which demonstrated strong predictive ability. Based on these findings, this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.

The prognostic value of the systemic immune-inflammation index (SII) for prostate cancer (PCa) patients receiving different treatments remains unclear. This research examined the relevance of SII in individuals undergoing radical prostatectomy (RP).

PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI) dat3 abases were used to search literature up to May 2024. The quality was evaluated with Newcastle-Ottawa Scale. Outcomes examined were associations between SII and overall survival (OS), biochemical recurrence-free survival (BFS), and cancer-specific survival (CSS). Pooled analysis, Egger's test, and sensitivity analysis were conducted using Review Manager 5.4.1 and Stata 15.1. The GRADE system was employed to evaluate and grade the evidence for each outcome. Subgroup analyses were performed for outcomes with significant heterogeneity to evaluate the possible confounders, if data were sufficient.

Out of 101 identified studies, eight studies involving 8,267 individuals were included. Patients with higher SII had shorter overall survival (HR: 1.89; 95% CI: 1.31-2.71; P = 0.0006), biochemical recurrence-free survival (HR: 1.55; 95% CI: 1.08-2.22; P = 0.02), and cancer-specific survival (HR: 3.63; 95% CI: 1.66-7.94; P = 0.001). The evidence for OS and CSS was rated very low-quality due to serious heterogeneity and/or imprecision. The prognostic value of SII for BFS was rated as low-quality evidence, given no serious risk observed. Subgroup analysis showed that, except for the subgroup aged >65 years (HR: 3.70; 95%CI: 0.91, 15.06, P=0.07), the prognostic value of SII for OS was not significant, but the prognostic value of SII for OS in other subgroups was still significant.

High SII was linked to shorter OS, BFS, and CSS in patients undergoing RP. However, the quality of the evidence provided by this study was low.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024558431.

In recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and have become a key therapeutic approach in cancer treatment. However, while ICIs activate the immune system, they can also induce immune-related adverse events (irAEs). Due to the variability in the frequency and severity of irAEs, clinical management faces a significant challenge in balancing antitumor efficacy with the risk of irAEs. Predicting and preventing irAEs during the early stages of treatment has become a critical research focus in cancer immunotherapy. This study aims to evaluate the predictive value of peripheral blood cell counts for irAEs.

Studies meeting the inclusion criteria were identified through database searches. The standardized mean difference (SMD) was used to compare continuous blood cell counts. For studies that did not provide adjusted odds ratios (ORs) and 95% confidence intervals (CIs), crude ORs for categorized blood cell counts were calculated. The study protocol was registered on PROSPERO (CRD42024592126).

The meta-analysis included 60 studies involving 16,736 cancer patients treated with ICIs. Compared to patients without irAEs, those experiencing irAEs had significantly higher baseline continuous ALC (SMD = 0.12, 95% CI = 0.01-0.24), while ANC (SMD = -0.18, 95% CI = -0.28 to -0.07) and PLR (SMD = -0.32, 95% CI = -0.60 to -0.04) were significantly lower. Similarly, categorized blood cell counts indicated that higher baseline ALC (OR = 2.46, 95% CI = 1.69-3.57) and AEC (OR = 2.05, 95% CI = 1.09-3.85), along with lower baseline NLR (OR = 0.64, 95% CI = 0.50-0.81) and PLR (OR = 0.63, 95% CI = 0.48-0.82), were associated with an increased risk of irAEs. Subgroup analysis further identified cutoff values for ALC (2×10^9/L), NLR (5 or 3), and PLR (180) as better predictors of irAEs.

Higher baseline ALC and AEC, along with lower baseline ANC, NLR, and PLR, are associated with an increased risk of irAEs. However, further research is needed to determine the optimal cutoff values and to explore the efficacy of blood cell counts in predicting specific types of irAEs.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024592126.

The tumor microenvironment (TME) is closely associated with the therapeutic response and clinical outcome of cancer drug therapies, which mainly include immunotherapy, chemotherapy and targeted therapy. Neutrophils that infiltrate tumors, also known as tumor-associated neutrophils (TANs), constitute a primary part of the TME. However, the functional importance of TANs in cancer drug therapy has long been overlooked because of their relatively short life span. Recent studies have shown that TANs play crucial protumoral or antitumoral roles in cancer drug treatment, largely because of their diversity and plasticity. This review describes the development, heterogeneity and recruitment of neutrophils in the context of cancer and emphasizes the role and mechanisms of TANs in cancer drug resistance. Additionally, several potential neutrophil-targeted strategies are discussed.

Hepatocellular carcinoma (HCC) is among the most prevalent malignant tumors, but the current staging system has limited efficacy in predicting HCC prognosis. The authors sought to develop and validate a nomogram model for predicting overall survival (OS) in HCC patients primarily undergoing surgery or loco-regional therapy. Patients diagnosed with HCC from January 2017 to June 2023 were enrolled in the study. The data were randomly split into a training cohort and a validation cohort. Utilizing univariate and multivariate Cox regression analyses, independent risk factors for OS were identified, and a nomogram model was constructed to predict patient survival. Therapy, body mass index, portal vein tumor thrombus, leukocyte, γ-glutamyl transpeptidase to platelet ratio, monocyte to lymphocyte ratio, and prognostic nutritional index were used to build the nomogram for OS. The nomogram demonstrated strong predictive ability, with high C-index values (0.745 for the training cohort and 0.650 for the validation cohort). ROC curves, calibration plots, and DCA curves all indicated satisfactory performance of the nomogram. Kaplan-Meier curve analysis showed a significant difference in prognosis between patients in the low- and high- risk groups. This nomogram provides precise survival predictions for HCC patients and helps identify individuals with varying prognostic risks, emphasizing the need for individualized follow-up and treatment plans.

In recent years, the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) have been considered potential predictors of survival outcomes in various solid tumors, including gastric cancer. However, there is a notable lack of research focusing on their prognostic implications specifically in the early stage of gastric cancer. This study aims to investigate the prognostic indicators of early gastric cancer (EGC), including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), SII, PNI, and lymph node metastasis (LNM).

In this retrospective analysis, we examined 490 patients diagnosed with EGC (pT1Nx). The peripheral blood indices of interest were SII, PNI, PLR, and NLR. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to determine optimal cutoff values and prognostic efficacy for each parameter. Additionally, Kaplan-Meier survival curves and multivariate Cox regression models were utilized to delineate independent prognostic factors.

The optimal cutoff values for SII and PNI were determined as 613.05 and 42.21, respectively. Patients in the low SII (SII-L) group demonstrated significantly higher 5-year Disease-Free Survival (DFS) and Overall Survival (OS) rates of 94.7% and 96.2%, compared to the high SII (SII-H) group (DFS: 78.7%; OS: 81.9%), with both differences proving statistically significant (P < 0.001, P < 0.001). Similarly, patients in the high PNI (PNI-H) group showed superior 5-year DFS (93.3%) and OS rates (95.1%) versus the low PNI (PNI-L) group (DFS: 71.4%; OS: 74.3%), also demonstrating statistical significance (P < 0.001, P < 0.001). Multivariate analysis identified SII, PNI, and LNM as independent prognostic factors for EGC. A combined analysis of SII, PNI, and LNM yielded a C-index of 0.723 (P = 0.008).

SII, PNI, and LNM are effective markers for predicting the survival outcomes of patients undergoing radical gastrectomy for EGC.

Oncolytic viruses are either naturally occurring or genetically engineered viruses that can activate immune cells and selectively replicate in and destroy cancer cells without damaging healthy tissues. Oncolytic virus therapy (OVT) represents an emerging treatment approach for cancer. In this review, we outline the properties of oncolytic viruses and then offer an overview of the immune cells and tumor microenvironment (TME) across various OVTs. A thorough understanding of the immunological mechanisms involved in OVTs could lead to the identification of novel and more effective therapeutic targets for cancer treatment.

The predictive accuracy of the preoperative neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with non-muscle-invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette-Guérin immunotherapy (BCG) after transurethral resection of the bladder tumor (TURBT) remains unknown. Therefore, the current study performed a systematic review and meta-analysis to examine the relationship between preoperative NLR and the prognosis of patients with NMIBC with intravesical BCG immunotherapy.

For this systematic review and meta-analysis, articles were retrieved from PubMed, Cochrane Library, Web of Science, and Embase databases from their inception to 14 May 2024. The role of NLR in predicting recurrence and progression in NMIBC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs).

Seven articles were included in this meta-analysis, involving 4,187 patients. An elevated NLR was significantly associated with recurrence (HR = 2.67, 95% CI = 1.34-5.32, P < 0.001) and progression (HR = 1.72, 95% CI = 1.13-2.60, P = 0.004) in patients with NMIBC with intravesical BCG immunotherapy.

This meta-analysis demonstrated that elevated preoperative NLR levels were significantly associated with recurrence and disease progression in patients with NMIBC who underwent intravesical BCG immunotherapy after TURBT.

https://inplasy.com/inplasy-2024-7-0058/, identifier 202470058.

Excessive neutrophil infiltration into the tumor microenvironment (TME) is an important factor that contributes to tumor overgrowth and limited immunotherapy efficacy. Neutrophils activate various receptors involved in tumor progression, while suppressing the infiltration and activity of cytotoxic T cells and creating optimal conditions for tumor growth. Therefore, the appropriate control of neutrophil infiltration is an effective strategy for tumor treatment. In the present study, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) inhibited tumor overgrowth by suppressing excessive neutrophil infiltration, resulting in >74.97 % reduction in tumor size in a Lewis lung carcinoma (LLC-1) mouse model. All subjects in the positive control group died during the 90-day survival period, whereas only four subjects in the PLAG treatment group survived. PLAG had a significantly higher tumor growth inhibitory effect and survival rate than other neutrophil infiltration-targeting inhibitors (e.g., Navarixin, lymphocyte antigen 6 complex locus G6D antibody [aLy6G]). The ability of PLAG to regulate neutrophil infiltration and inhibit tumor growth depends on thioredoxin-interacting protein (TXNIP). In tumors lacking TXNIP expression, PLAG failed to control neutrophil infiltration and infiltration-related factor release, and the inhibitory effect of PLAG on tumor growth was reduced. PLAG-mediated inhibition of neutrophil infiltration enhances the efficacy of immune checkpoint inhibitors (ICIs), increasing the antitumor efficacy and survival rate by 30 %. In conclusion, PLAG could be a novel alternative to anti-tumor drugs that effectively targets excessive neutrophil infiltration into cancer tissues.

Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game-changing drug delivery platform. In fact, poly(α-hydroxy acids) such as polylactide (PLA), poly(lactide-co-glycolide) (PLGA), and poly(ε-caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface-functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state-of-the-art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re-evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester-based NPs closer to clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC).

120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils' chemokines in OSCC using a real-time PCR, western blotting.

Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05).

Our study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition to participating in the body's inflammatory response, NE also plays an important role in cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), and change the tumor microenvironment (TME) to promote tumor progression. Concurrently, NE promotes systemic treatment resistance by inducing EMT. However, it can also selectively kill cancer cells and attenuate tumor development. Sivelestat is a specific NE inhibitor that can be used in the perioperative period of esophageal cancer patients to reduce the incidence of postoperative complications after esophagectomy. In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Meanwhile, targeting the human antibody domains and fragments of NE is also a new way to treat cancer and inflammation-related diseases. This review provides valuable insights into the role of NE in cancer treatment. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies.

Preoperative inflammatory factors and nutritional status are strongly associated with the prognosis of a variety of cancers. We explored the relationship between preoperative lymphocytes, neutrophils and albumin (LANR) and progression-free survival in breast cancer patients.

The clinical and follow-up data of 200 breast cancer patients were retrospectively analyzed in this study, and the value of LANR was determined as follows: LANR, lymphocytes × albumin/neutrophils. ROC curves, COX proportional risk regression analysis and subgroup analysis were used to assess the prognostic value of LANR in progression-free survival of breast cancer patients.

The median age of the patients was 55.5 years (range 50-62 years). The median follow-up time was 46 months (range 33-55 months). In progression-free survival, the area under the LANR curve was 0.748 and the HR (95% CI) was 0.035 (0.679-0.817). LANR was associated with age (p = 0.02), positive axillary lymph nodes (p < 0.001), TNM stage (p < 0.001) and human epidermal growth factor receptor 2(p = 0.004). The results indicated that preoperative LANR may be a reliable predictor of progression-free survival in patients with operable breast cancer.

LANR may be an essential predictor for breast cancer patients and provides a therapeutic basis for clinicians and patients.

Triple negative breast cancers (TNBC) are characterized by a poor prognosis and a lack of targeted treatments. Their progression depends on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Although adipocytes, the primary stromal cells of the breast, have been determined to be plastic in physiology and cancer, the tumor-derived molecular mediators of tumor-adipocyte crosstalk have not been identified yet. In this study, we report that the crosstalk between TNBC cells and adipocytes in vitro beyond adipocyte dedifferentiation, induces a unique transcriptional profile that is characterized by inflammation and pathways that are related to interaction with the tumor microenvironment. Accordingly, increased cancer stem-like features and recruitment of pro-tumorigenic immune cells are induced by this crosstalk through CXCL5 and IL-8 production. We identified serum amyloid A1 (SAA1) as a regulator of the adipocyte reprogramming through CD36 and P2XR7 signaling. In human TNBC, SAA1 expression was associated with cancer-associated adipocyte infiltration, inflammation, stimulated lipolysis, stem-like properties, and a distinct tumor immune microenvironment. Our findings constitute evidence that the interaction between tumor cells and adipocytes through the release of SAA1 is relevant to the aggressiveness of TNBC.

TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer's varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines.

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically 'cold' tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in 'cold' tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various 'cold' tumors. Understanding the intricacies of the TME in 'cold' tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.

Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC).

While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown.

A multicenter, retrospective-prospective Italian study.

We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables.

We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively).

Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i.

The immune system defines a complex network of tissues and cell types that orchestrate responses across the body in a dynamic manner. The local and systemic interactions between immune and cancer cells contribute to disease progression. Lymphocytes are activated in lymph nodes, traffic through the periphery, and impact cancer progression through their interactions with tumor cells. As a result, therapeutic response and resistance are mediated across tissues, and a comprehensive understanding of lymphocyte dynamics requires a systems-level approach. In this review, we highlight experimental and computational methods that can leverage the study of leukocyte trafficking through an immunomics lens and reveal how adaptive immunity shapes cancer.

Cancer is a complex and dynamic disease, initiated by a multitude of intrinsic mutations and progressed with the assistance of the tissue microenvironment, encompassed by stromal cells including immune cell infiltration. The novel finding that tumors can evade anti-cancer immune functions shaped the field of immunotherapy, which has been a revolutionary approach for the treatment of cancers. However, the development of predominantly T cell-targeted immunotherapy approaches, such as immune checkpoint inhibition, also brought about an accumulation of evidence demonstrating other immune cell drivers of tumor progression, such as innate immune cells and notably, neutrophils. In the past decade, neutrophils have emerged to be primary mediators of multiple cancer types and even in recent years, are gaining attention for their potential use in the next generation of immunotherapies. Here, we review current immunotherapy strategies and thoroughly discuss the roles of neutrophils in cancer and novel neutrophil-targeted methods for treating cancer.

Role of neutrophils in shaping the tumor microenvironment is well known in oral squamous cell carcinoma (OSCC). However, neutrophil microabscess (NM) formation within the tumor islands is distinctive phenomenon and has never been investigated in the literature. This pilot observational study identifies the incidence of NM in OSCC and its clinicopathologic correlation as a platform for the future studies.

A retrospective study was carried out on archival specimens of 121 cases of surgically excised OSCC specimens for identification of NM formations within the tumor islands using compound microscope. Mean NM density was calculated based on the quantification done at five randomly selected hotspots.

Out of total 121 cases of OSCC, thirteen (10.74%) cases showed a frank evidence of NM within tumor islands. The hotspot analysis showed that the NM density ranges from 2 to 7 with mean of 3.76 ± 1.39 per high power field. NM density was higher in moderately differentiated OSCC (3.76 ± 1.93) than well differentiated (3.76 ± 1.93) however the differences were not statistically significant (p = 0.165). Similarly, higher NM density was reported in advanced T stage, lymph node involvement, advanced TNM stage and lymphovascular invasion, however, the results were statistically insignificant.

There is evidence of NM formation in the tumor islands of OSCC, however their exact role as a prognosticator needs further exploration with large sample size and follow-up data.

Background and Objectives: To assess the potential prognostic role of the systemic immune-inflammation index (SII) in predicting oncological outcomes in a cohort of patients treated with radical cystectomy (RC). Materials and Methods: From 2016 to 2022, a retrospective monocentric study enrolled 193 patients who were divided into two groups based on their SII levels using the optimal cutoff determined by the Youden index. The SII was obtained from a preoperative blood test approximately one month before RC. Univariable and multivariable logistic regression analyses were conducted to investigate the capacity of SII to predict lymph node invasion (N), advanced pT stage (pT3/pT4), and locally advanced condition at the time of RC. Multivariable Cox regression models adjusted for preoperative and postoperative features were used to analyze the prognostic effect of SII on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The optimal cutoff value of the SII was 640.27. An elevated SII was seen in 113 (58.5%) patients. Using the multivariable preoperative logistic regression models, an elevated SII was correlated with nodal invasion (N; p = 0.03), advanced pT stage (p = 0.04), and locally advanced disease (p = 0.005), with enhancement of AUCs for predicting locally advanced disease (p = 0.04). In multivariable Cox regression models that considered preoperative clinicopathologic factors, an elevated SII was linked to poorer RFS (p = 0.005) and OS (p = 0.01). Moreover, on multivariable Cox regression postoperative models, a high SII was linked to RFS (p = 0.004) and to OS (p = 0.01). Conclusions: In this monocentric retrospective study, higher preoperative SII values predicted worse oncological outcomes in patients with bladder cancer (BCa) who underwent RC.

The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM.

The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC.

Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively.

This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

The systemic immune-inflammation index (SII) has emerged as a promising marker predicting the prognosis of some cancers, while its role in urothelial carcinoma (UC) remains uncertain, especially in upper urinary tract urothelial carcinoma (UTUC). This meta-analysis aimed to investigate the association of SII with the prognosis of UC and the response to intravesical Bacillus Calmette-Guerin (BCG) therapy of non-muscle invasive bladder cancer (NMIBC).

A systematic search in PubMed, Embase, Web of Science, and the Cochrane Library was performed to identify relevant studies. The extracted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate the association between SII and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of patients with UC. Additionally, we pooled odds ratios (ORs) and 95% CIs to assess the relationship between SII and BCG response in patients with NMIBC. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity.

Twenty studies comprising a total of 12,645 patients were eligible. This meta-analysis revealed that high SII levels independently increased the risk of OS (HR 1.55, 95%CI 1.25-1.92), CSS (HR 1.82, 95%CI 1.36-2.45), and RFS (HR 1.26, 95% CI 1.18-1.35) in patients with UC, including those with upper tract urothelial carcinoma. Additionally, elevated SII levels could predict a lower response to intravesical BCG treatment (OR 0.18, 95%CI 0.07-0.45) and higher disease recurrence (HR 1.61, 95%CI 1.31-1.98) in patients with NMIBC. Furthermore, elevated SII levels were positively associated with advanced age, lymphovascular invasion, hydronephrosis, and high tumor grade and stage (pT ≥ 3).

Elevated preoperative SII levels are associated with poor survival outcomes in patients with UC, as well as worse response to BCG treatment in patients with NMIBC. Therefore, SII can serve not only as an independent prognostic predictor of patients with UC but also as a guide for BCG therapy in NMIBC.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023409077, identifier CRD42023409077.

Since the incidence of gouty arthritis (GA) exhibits yearly increases, accurate assessment and early treatment have significant values for improving disease conditions and monitoring prognosis. Neutrophil to lymphocyte ratio (NLR) is a common indicator in blood routine, which has the characteristics of easy access and low cost. In recent years, NLR has been proven to be an effective indicator for guiding the diagnosis, treatment, and prognosis of various diseases. Moreover, NLR has varying degrees of relationship with various inflammatory biomarkers, which can affect and reflect the inflammatory response in the body. This paper reviews the independent value of NLR for GA and its underlying molecular pathological mechanisms, intending to contribute to the further application of NLR.

Brain metastasis (BM) is a common event during the development of many cancers, and is also one of the main causes of death of patients. Stereotactic radiosurgery (SRS) is an effective treatment for BM. The prognostic effects of various clinical factors on local control (LC) and overall survival (OS) after SRS treatment are still unclear. The purpose of this study is to retrospectively analyze the intracranial progression free survival (iPFS) and OS of patients receiving SRS treatment, and explore the relationship between various clinical characteristics and patient prognosis.

We collected the clinical information of patients who were diagnosed with BM and received SRS treatment in our center between 2018 and 2021. Univariate and multivariate Cox regression analysis and KM analysis for iPFS and OS were conducted in R software to investigate the prognostic effects of clinical characteristics.

In total, 183 patients that received SRS in our center were enrolled in the cohort. The median iPFS for all patients was 8.87 months (95% CI 6.9-10.6), and the median OS was 16.5 months (95% CI 12.9-20.7). BM number >  = 5 (HR 1.965 [95% CI 1.381-2.796], p < 0.001, FDR-corrected p < 0.001) was found to be strong predictor for shorter iPFS and OS. Subgroup analysis showed that patients with cumulative intracranial tumor volume (CITV) >  = 2.14 cm3 and number >  = 5 had shortest iPFS (P < 0.001) and OS (P = 0.007), compared with other subgroups. For patients with more than 5 BMs, SRS plus whole brain radiotherapy (WBRT) could achieve better local control, compared with SRS alone group (P = 0.0357). Peripheral blood inflammation indicators were associated with the prognosis of BM patients in univariate Cox analysis, but not in multivariate Cox analysis.

BM number is an independent prognostic factor for BM patients. The prognosis of patients in the subgroup with larger CITV and more BM is the worst. For patients with more than 5 BM, the combination of SRS and WBRT can improve the local control, but cannot prolong the OS.

The newly discovered pan-immune-inflammation value (PIV) has been illustrated to have good prognostic value for cancer patient prognosis. However, the prognostic usefulness of PIV in breast cancer patients is unknown. As a result, to aid the clinic in providing a distinctive and trustworthy biomarker to better assess breast cancer patient's prognosis, we conducted this meta-analysis to investigate the relationship between PIV and the survival of breast cancer patients.

We conducted a systematic search of Pubmed, Embase, the Cochrane Library, and the CNKI databases to screen for eligible studies published up to April 2023. Outcomes included overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR). The hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the indicators. STATA 15.0 software was used to perform meta-analysis, sensitivity analysis, and publication bias analysis.

A total of eight articles, involving 2953 patients, met the inclusion criteria and were included in this meta-analysis. The results showed that patients with higher PIV levels had a significantly shorter OS (HR: 2.045, 95% CI: 1.355-3.086, P = 0.001) and PFS (HR: 1.466, 95% CI: 1.163-1.848, P = 0.001). Besides, the PIV value was negatively correlated with the efficacy of neoadjuvant chemotherapy. Sensitivity analysis showed that the results of this study were reliable and stable.

PIV has a good prognostic value in breast cancer patients and is expected to be a prognostic biomarker for breast cancer.

Despite significant advances in diagnostic methods and treatment strategies, the prognosis for patients with advanced colon cancer remains poor, and mortality rates are often high due to metastasis. Increasing evidence showed that it is of significant importance to investigate how the tumor microenvironment participates in the development of colorectal cancer (CRC). In this manuscript, neutrophils were sequentially stimulated with all-trans retinoic acid and transforming growth factor-β in turn to induce the neutrophil polarization. Differentially expressed miRNA in neutrophil exosomes have been sequenced by microarray profile, and the effect of N2-like neutrophil-derived exosomal miR-4780 on epithelial-mesenchymal transition (EMT) and angiogenesis was investigated. In our results, we found that neutrophils were enriched in CRC tumor tissue and that CD11b expression correlated with tumor site and serous membrane invasion. At the same time, we demonstrated that internalization of N2 exosomes exacerbated the viability, migration, and invasion of CRC cell lines and inhibited apoptosis. To further investigate the molecular mechanism, we analyzed the miRNA expression profile in the N2-like neutrophils, which led to the selection of hsa-miR-4780 for the subsequent experiment. The overexpression of miR-4780 from N2-like neutrophil-derived exosomes exacerbated EMT and angiogenesis. Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines. CRC with liver metastasis model also validated that aberrant expression of miR-4780 in N2-like neutrophil exosomes exacerbated tumor metastasis and development of tumor via EMT and angiogenesis. In conclusion, our current findings reveal an important mechanism by which mR-4780 from N2-like neutrophil exosomes exacerbates tumor metastasis and progression via EMT and angiogenesis.

There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC).

We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA).

A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model.

We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation.

Breast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B-cell heterogeneity at single-cell resolution and its clinical significance with TLS in BC need to be explored further.

Primary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single-cell transcriptome sequencing and bioinformatics analysis.

Based on the usual markers, the single-cell transcriptome profiles were classified into various clusters. A thorough single-cell study was conducted with a focus on tumour-infiltrating B cells (TIL-B) and tumour-associated neutrophils (TAN). TIL-B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL-B infiltration are positively correlated, and at the same time, compared with TLS-high, TAN and TIL-B in TLS-low group are significantly positively correlated.

In conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single-cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of many cancer types, including head and neck cancers (HNC). When checkpoint and partner proteins bind, these send an "off" signal to T cells, which prevents the immune system from destroying tumor cells. However, in HNC, and indeed many other cancers, more people do not respond and/or suffer from toxic effects than those who do respond. Hence, newer, more effective approaches are needed. The challenge to durable therapy lies in a deeper understanding of the complex interactions between immune cells, tumor cells and the tumor microenvironment. This will help develop therapies that promote lasting tumorlysis by overcoming T-cell exhaustion. Here we explore the strengths and limitations of current ICI therapy in head and neck squamous cell carcinoma (HNSCC). We also review emerging small-molecule immunotherapies and the growing promise of neutrophil extracellular traps in controlling tumor progression and metastasis.

Cholangiocarcinoma is a highly aggressive cancer arising from the bile ducts. The limited effectiveness of conventional therapies has prompted the search for new approaches to target this disease. Recent evidence suggests that distinct programmed cell death mechanisms, namely, apoptosis, ferroptosis, pyroptosis and necroptosis, play a critical role in the development and progression of cholangiocarcinoma. This review aims to summarize the current knowledge on the role of programmed cell death in cholangiocarcinoma and its potential implications for the development of novel therapies. Several studies have shown that the dysregulation of apoptotic signaling pathways contributes to cholangiocarcinoma tumorigenesis and resistance to treatment. Similarly, ferroptosis, pyroptosis and necroptosis, which are pro-inflammatory forms of cell death, have been implicated in promoting immune cell recruitment and activation, thus enhancing the antitumor immune response. Moreover, recent studies have suggested that targeting cell death pathways could sensitize cholangiocarcinoma cells to chemotherapy and immunotherapy. In conclusion, programmed cell death represents a relevant molecular mechanism of pathogenesis in cholangiocarcinoma, and further research is needed to fully elucidate the underlying details and possibly identify therapeutic strategies.

As the most abundant white blood cells in humans, neutrophils play a key role in acute and chronic inflammation, suggesting that these cells are a key component of targeted therapies for various inflammation-related diseases. Specific enzyme-responsive or specific ligand-modified polymer nanoparticles are beneficial for improving drug efficacy, reducing toxicity, and enhancing focal site retention. However, there remain significant challenges in biomedical applications of these synthetic polymer nanoparticles, mainly due to their rapid clearance by the reticuloendothelial system. In recent years, biomimetic drug delivery systems such as neutrophils acting directly as drug carriers or neutrophil-membrane-coated nanoparticles have received increasing attention due to the natural advantages of neutrophils. Thus, neutrophil-targeted, neutrophil-assisted, or neutrophil-coated nanoparticles exhibit a prolonged blood circulation time and improved accumulation at the site of inflammation. Despite recent advancements, further clinical research must be performed to evaluate neutrophil-based delivery systems for future biomedical application in the diagnosis and treatment of related inflammatory diseases. In this review, we have summarized new exciting developments and challenges in neutrophil-mediated drug delivery strategies for treating inflammation-related diseases.