The historical context of phytotherapy affects its potential as therapeutic products, and bioactive metabolites are crucial to the pharmacological effects, safety and effectiveness of alternative medicines.

Phytotherapy is of great interest to cancer patients. Therefore, the purpose of this study was to gather publications about the interactions between chemotherapy and phytotherapeutics, medicinal plants, and similar formulations. To find publications published between January 2015 and January 2025, a MEDLINE PubMed search was conducted.

Several scientists and medical specialists have been looking into the potential of natural items to heal microbial cancer and chemotherapy-related adverse effects. The main factor influencing phytochemicals anticancer effectiveness is their ability to target a variety of pathways, including antimutagenic, antioxidant, and antiproliferative qualities. They can also regulate the host immune response to cancer by improving the surveillance of lymphocytes in cancer cells and lowering the inflammatory milieu. Because carcinogenesis is complex and involves a wide range of factors and signaling cascades, phytochemicals that target several targets may be useful anticancer drugs.

Acute respiratory distress syndrome (ARDS) is a severe complication associated with a high mortality rate in patients with sepsis. Early identification of patients with sepsis at high risk of developing ARDS is crucial for timely intervention, optimization of treatment strategies, and improvement of clinical outcomes. However, traditional risk prediction methods are often insufficient. This study aimed to develop a machine learning (ML) model to predict the risk of ARDS in patients with sepsis using circulating immune cell parameters and other physiological data.

Clinical data from 10,559 patients with sepsis were obtained from the MIMIC-IV database. Principal component analysis (PCA) was used for dimensionality reduction and to comprehensively evaluate the models' predictive capabilities, we used several ML algorithms, including decision trees, k-nearest neighbors (KNN), logistic regression, naive Bayes, random forests, neural networks, XGBoost, and support vector machines (SVM) to predict ARDS risk. The model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 score. Shapley additive explanations (SHAP) were used to interpret the contribution of individual features to model predictions.

Among all models, XGBoost showed the best performance with an AUC of 0.764. Feature importance analysis revealed that mean arterial pressure, monocyte count, neutrophil count, pH, and platelet count were key predictors of ARDS risk in patients with sepsis. The SHAP analysis provided further information on how these features contributed to the model's predictions, aiding in interpretability and potential clinical applications.

The XGBoost model using circulating immune cell parameters accurately predicted the risk of ARDS in patients with sepsis. This model could be a useful tool for the early identification of high-risk patients and timely intervention; however, further validation and integration into clinical practice are required.

The genomic landscape of cancer cells is complex and heterogeneous, with aberrant DNA methylation being a common observation. Growing evidence indicates that oxidants produced from immune cells may interact with epigenetic processes, and this may represent a mechanism for the initiation of altered epigenetic patterns observed in both precancerous and cancerous cells. Around 20% of cancers are linked to chronic inflammatory conditions, yet the precise mechanisms connecting inflammation with cancer progression remain unclear. During chronic inflammation, immune cells release oxidants in response to stimuli, which, in high concentrations, can cause cytotoxic effects. Oxidants are known to damage DNA and proteins and disrupt normal signalling pathways, potentially initiating a sequence of events that drives carcinogenesis. While research on the impact of immune cell-derived oxidants on DNA methylation remains limited, this mechanism may represent a crucial link between chronic inflammation and cancer development. This review examines current evidence on inflammation-associated DNA methylation changes in cancers related to chronic inflammation.

Tumor microenvironment (TME) denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. Interactions between cancer cells, immune cells, stromal cells, and the extracellular matrix within the TME create a dynamic ecosystem that can either promote or hinder tumor growth and spread. The TME plays a pivotal role in either promoting or inhibiting tumor growth and dissemination, making it a critical factor to consider in the development of effective cancer therapies. Understanding the intricate interplay within the TME is crucial for devising effective cancer therapies. Combination therapies involving inhibitors of immune checkpoint blockade (ICB), and/or chemotherapy now offer new approaches for cancer therapy. However, it remains uncertain how to best utilize these strategies in the context of the complex tumor microenvironment. Oncogene-driven changes in tumor cell metabolism can impact the TME to limit immune responses and present barriers to cancer therapy. Cellular and acellular components in tumor microenvironment can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Components in the TME can reprogram tumor behavior and influence responses to treatments, facilitating immune evasion, nutrient deprivation, and therapeutic resistance. Moreover, the TME can influence angiogenesis, promoting the formation of blood vessels that sustain tumor growth. Notably, the TME facilitates immune evasion, establishes a nutrient-deprived milieu, and induces therapeutic resistance, hindering treatment efficacy. A paradigm shift from a cancer-centric model to a TME-centric one has revolutionized cancer research and treatment. However, effectively targeting specific cells or pathways within the TME remains a challenge, as the complexity of the TME poses hurdles in designing precise and effective therapies. This review highlights challenges in targeting the tumor microenvironment to achieve therapeutic efficacy; explore new approaches and technologies to better decipher the tumor microenvironment; and discuss strategies to intervene in the tumor microenvironment and maximize therapeutic benefits.

The COVID-19 pandemic has led to widespread long-term complications, known as post-COVID conditions (PCC), particularly affecting vulnerable populations such as cancer patients. This study aims to predict the incidence of PCC in hospitalised cancer patients using the data from a longitudinal cohort study conducted in four major university hospitals in Moscow, Russia.

Clinical data have been collected during the acute phase and follow-ups at 6 and 12 months post-discharge. A total of 49 clinical features were evaluated, and machine learning classifiers including logistic regression, random forest, support vector machine (SVM), k-nearest neighbours (KNN), and neural network were applied to predict PCC.

Model performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. KNN demonstrated the highest predictive performance, with an AUC of 0.80, sensitivity of 0.73, and specificity of 0.69. Severe COVID-19 and pre-existing comorbidities were significant predictors of PCC.

Machine learning models, particularly KNN, showed some promise in predicting PCC in cancer patients, offering the potential for early intervention and personalised care. These findings emphasise the importance of long-term monitoring for cancer patients recovering from COVID-19 to mitigate PCC impact.

The pivotal role of type 1 conventional dendritic cells (cDC1s) in the field of dendritic cell (DC)-based tumor immunotherapies has been gaining increasing recognition due to their superior antigen cross-presentation abilities and essential role in modulating immune responses. This review specifically highlights the C-type lectin receptor family 9 member A (Clec9a or DNGR-1), which is exclusively expressed on cDC1s and plays a pivotal role in augmenting antigen cross-presentation and cytotoxic T lymphocyte (CTL) responses while simultaneously mitigating off-target effects. These effects include the enhancement of the cDC1s cross-presentation, reducing autoimmune responses and systemic inflammation, as well as preventing the non-specific activation of other immune cells. Consequently, these actions may contribute to reduced toxicity and enhanced treatment efficacy in immunotherapy. The exceptional ability of Clec9a to cross-present dead cell-associated antigens and enhance both humoral and CTL responses makes it an optimal receptor for DC-based strategies aimed at strengthening antitumor immunity. This review provides a comprehensive overview of the molecular characterization, expression, and signaling mechanisms of Clec9a. Furthermore, it discusses the role of Clec9a in the induction and functional activation of Clec9a+ cDC1s, with a particular focus on addressing the challenges related to off-target effects and immune tolerance in the development of tumor vaccines. Additionally, this review explores the potential of Clec9a-targeted approaches to enhance the immunogenicity of tumor vaccines and addresses the utilization of Clec9a as a delivery target for specific agonists (such as STING agonists and αGC) to enhance their therapeutic effects. This novel approach leverages Clec9a's capacity to improve the precision and efficacy of these immunomodulatory molecules in tumor treatment. In summary, this review presents compelling evidence positioning Clec9a as a promising target for DC-based tumor immunotherapy, capable of enhancing the efficacy of vaccines and immune responses while minimizing adverse effects.

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, remains a leading cause of cancer-related mortality worldwide, particularly among elderly individuals. The phenomenon of immunosenescence, characterized by the progressive decline in immune cell functionality with aging, plays a pivotal role in NSCLC progression and contributes to the diminished efficacy of therapeutic interventions in older patients. Immunosenescence manifests through impaired immune surveillance, reduced cytotoxic responses, and increased chronic inflammation, collectively fostering a pro-tumorigenic microenvironment. This review provides a comprehensive analysis of the molecular, cellular, and genetic mechanisms of immunosenescence and its impact on immune surveillance and the tumor microenvironment (TME) in NSCLC. We explore how aging affects various immune cells, including T cells, B cells, NK cells, and macrophages, and how these changes compromise the immune system's ability to detect and eliminate tumor cells. Furthermore, we address the challenges posed by immunosenescence to current therapeutic strategies, particularly immunotherapy, which faces significant hurdles in elderly patients due to immune dysfunction. The review highlights emerging technologies, such as single-cell sequencing and CRISPR-Cas9, which offer new insights into immunosenescence and its potential as a therapeutic target. Finally, we outline future research directions, including strategies for rejuvenating the aging immune system and optimizing immunotherapy for older NSCLC patients, with the goal of improving treatment efficacy and survival outcomes. These efforts hold promise for the development of more effective, personalized therapies for elderly patients with NSCLC.

Immunity suffers a function deficit during aging, and the incidence of cancer is increased in the elderly. However, most cancer models employ young mice, which are poorly representative of adult cancer patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine and generation of TCF1+-stem-cell-like T cells (scTs) by cyclophosphamide significantly improved anti-PD-1 efficacy in anti-PD1-resistant models like Triple-Negative Breast Cancer (TNBC) and Non-Hodgkin's Lymphoma (NHL), due to T-cell-mediated tumor killing. Here, we describe the effect of TT on TNBC growth and on tumor-microenvironment (TME) of young (6-8w, representative of human puberty) versus adult (12 m, representative of 40y-humans) mice. TT-efficacy was similar in young and adults, as CD8+ scTs were only marginally reduced in adults. However, single-cell analyses revealed major differences in the TME: adults had fewer CD4+ scTs, B-naïve and NK-cells, and more memory-B-cells. Cancer-associated-fibroblasts (CAF) with an Extracellular Matrix (ECM) deposition-signature (Matrix-CAFs) were more common in young mice, while pro-inflammatory stromal populations and myofibroblasts were more represented in adults. Matrix-CAFs in adult mice displayed decreased ECM-remodeling abilities, reduced collagen deposition, and a different pattern of interactions with the other cells of the TME. Taken together, our results suggest that age-dependent differences in the TME should be considered when designing preclinical studies.

Thyroid carcinoma (THCA) is the most common cancer of the endocrine system. Natural killer (NK) cell play an important role in tumor immune surveillance. The aim of this study was to explore the possible molecular mechanisms involved in NK cell in THCA to help the management and treatment of the disease.

All data were downloaded from public databases. Candidate hub genes associated with NK cell in THCA were identified by limma, WGCNA and singleR packages. Functional enrichment analysis was performed on the candidate hub genes. Hub genes associated with NK cell were identified by Pearson correlation analysis. The mRNA-miRNA-lncRNA and transcription factors (TF) networks were constructed and the drug was predicted.

The infiltration level of NK cell in THCA tissues was higher than that in paracancerous tissues. KEGG functional enrichment analysis only obtained two signaling pathways, thyroid hormone synthesis and mineral absorption. CTSC, FN1, SLC34A2 and TMSB4X identified by Pearson correlation analysis were considered as the hub genes. Receiver operating characteristic analysis suggested that hub genes may be potential diagnostic biomarkers. In mRNA-miRNA-lncRNA network, FN1 had the highest correlation with IQCH-AS1, and IQCH-AS1 was also correlated with hsa-miR-543. In addition, FN1 and RUNX1 were also found to have the highest correlation in TF network. Finally, NK cell-related drugs belinostat and vorinostat were identified based on ASGARD.

The identification of important signaling pathways, molecules and drugs provides potential research directions for further research in THCA and contributes to the development of diagnostic and therapeutic approaches for this disease.

Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity are known and used, they often fail to achieve satisfactory long-term patient outcomes and survival. Recently, immunotherapy has shown success in patients by harnessing important interactions between the immune system and cancer. However, many of these therapies lead to frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, in severe cases, fatalities. New therapeutic approaches like intratumoral immunotherapy, characterized by reduced side effects, cost, and systemic toxicity, offer promising prospects for future applications in clinical oncology. In the context of locally advanced or metastatic cancer, combining diverse immunotherapeutic and other treatment strategies targeting multiple cancer hallmarks appears crucial. Such combination therapies hold promise for improving patient outcomes and survival and for promoting a sustained systemic response. This review aims to provide a current overview of immunotherapeutic approaches, specifically focusing on the intratumoral administration of drugs in patients with locally advanced and metastatic cancers. It also explores the integration of intratumoral administration with other modalities to maximize therapeutic response. Additionally, the review summarizes recent advances in intratumoral immunotherapy and discusses novel therapeutic approaches, outlining future directions in the field.

The immune system is intricately interconnected with all other bodily systems. As individuals age, the immune system undergoes changes known as immunosenescence, increasing susceptibility to disease, and contributing significantly to the morbidity and mortality observed in older populations. Immunosenescence drives systemic aging and therefore represents a key therapeutic target to extend healthy aging. In recent years, the extensive application of omics technologies has broadened our understanding of aging and immunity, necessitating a comprehensive database to encapsulate these advancements and deepen our insights into immune aging in the era of artificial intelligence. The Immunosenescence Inventory is a pioneering database designed to provide a multidimensional and integrative view of the aging immune system. By leveraging cutting-edge omics technologies and analytical tools, Immunosenescence Inventory offers a comprehensive resource for researchers to explore the intricate relationship between immunosenescence and age-related health outcomes. Furthermore, the database, which aids in the creation of diagnostic tools for immune aging conditions, is now publicly available at https://ngdc.cncb.ac.cn/iaa/home.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but they can induce immune-related adverse events, including immune checkpoint inhibitor-associated pneumonia (CIP), a severe lung complication. CIP, particularly Grades 3-4, is associated with poor prognosis, indicating a critical need for research on this issue. Our study aimed to investigate the risk factors and biomarkers associated with severe CIP in lung cancer patients treated with ICIs, where OS represents overall survival and PFS denotes progression-free survival.

We conducted a retrospective analysis of 106 lung cancer patients with CIP at the First Affiliated Hospital of Zhejiang University from 2019 to 2023, categorized into four severity grades.

The median time to onset of CIP was 5.17 months. Patients with Grade 3-4 CIP had a median PFS of 6.5 months and OS of 11.2 months. Univariate analysis identified phosphocreatine kinase below 61.5 U/l, Forced Vital Capacity (FVC) below 1.96, and BMI below 21.26 as predictive factors for Grades 3-4 CIP. Multivariate analysis confirmed that a decreased FVC was a significant predictor.

A decreased FVC below 1.96 emerged as a predictive factor for Grades 3-4 CIP, highlighting the importance of monitoring FVC in patients receiving ICIs.

The high prevalence of drug resistance, relapse, and unfavorable response rate of conventional cancer therapies necessitate the development of more efficient treatment modalities. Immunotherapy represents a novel therapeutic approach to cancer treatment in which the immune system's potential is harnessed to recognize and eliminate tumor cells. mRNA cancer vaccines, as a burgeoning field of immunotherapy, have recently drawn particular attention, and among mRNAs encoding tumor-associated antigens, tumor-specific antigens, and immune stimulatory factors, the latter has been relatively less explored. These immunostimulatory mRNAs encode a range of proteins, including stimulatory ligands, receptors, enzymes, pro-inflammatory cytokines, and inhibitory binding proteins, which collectively augment the host immune system's ability against cancerous cells. In this review, we aimed to provide a comprehensive account of mRNA-based cancer vaccines encoding immune stimulants, encompassing their current status, mechanisms of action, delivery strategies employed, as well as recent advances in preclinical and clinical studies. The potential challenges, strategies and future perspectives have also been discussed.

This study describes associations between immune cell types and cancer risk in a Black population; elevated regulatory T-cell proportions that were associated with increased overall cancer and lung cancer risk, and elevated memory B-cell proportions that were associated with increased prostate and all cancer risk.

Radiotherapy has played an essential role in cancer treatment for over a century, and remains one of the best-studied methods of cancer treatment. Because of its close links with the physical sciences, it has been the subject of extensive quantitative mathematical modelling, but a complete understanding of the mechanisms of radiotherapy has remained elusive. In part this is because of the complexity and range of scales involved in radiotherapy-from physical radiation interactions occurring over nanometres to evolution of patient responses over months and years. This review presents the current status and ongoing research in modelling radiotherapy responses across these scales, including basic physical mechanisms of DNA damage, the immediate biological responses this triggers, and genetic- and patient-level determinants of response. Finally, some of the major challenges in this field and potential avenues for future improvements are also discussed.

The incidence of autoimmune diseases and breast cancer is significantly higher in women compared to men. Previous observational studies have not conclusively determined the relationship between these two conditions. This study utilizes the Mendelian randomization approach to investigate the genetic association between autoimmune diseases and breast cancer.

Two-sample Mendelian randomization was conducted on a European population using the GWAS database. The inverse variance-weighted method served as the primary analytical approach. The MR-PRESSO test was applied to detect horizontal pleiotropy. To ensure result robustness, the FDR correction method was used.

The study revealed that Sjögren's syndrome lowers the overall risk of breast cancer (OR 0.96, 95% CI [0.93-0.99], p = 0.011). Idiopathic inflammatory myopathy shows a protective effect against overall breast cancer (OR 0.98, 95% CI [0.97-0.99], p = 0.035). An association was identified between rheumatoid arthritis and overall breast cancer (OR 0.98, 95% CI [0.96-1.00], p = 0.050). No causal link was found between systemic lupus erythematosus, systemic sclerosis, and overall breast cancer. The study also suggests that Sjögren's syndrome, rheumatoid arthritis, and idiopathic inflammatory myopathy might reduce the risk of developing HER + breast cancer. Specifically, Sjögren's syndrome (OR = 0.90, 95% CI [0.83-0.98], p = 0.02), rheumatoid arthritis (OR = 0.94, 95% CI [0.91-0.98], p = 0.006), and idiopathic inflammatory myopathy (OR = 0.96, 95% CI [0.93-0.99], p = 0.036). Additionally, systemic lupus erythematosus was found to lower the risk of HER- breast cancer (OR = 0.95, 95% CI [0.91-0.99], p = 0.046). The study did not establish a causal relationship between these five autoimmune diseases and ER + or ER- breast cancer.

This study found that autoimmune diseases may act as protective factors against breast cancer risk.

5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (λ = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 μg/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 ± 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 μg/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.

Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.

Early detection can significantly reduce mortality due to lung cancer. Presented here is an approach for developing a blood-based screening panel based on clonal hematopoietic mutations. Animal model studies suggest that clonal hematopoietic mutations in tumor infiltrating immune cells can modulate cancer progression, representing potential predictive biomarkers. The goal of this study was to determine if the clonal expansion of these mutations in blood samples could predict the occurrence of lung cancer. A set of 98 potentially pathogenic clonal hematopoietic mutations in tumor infiltrating immune cells were identified using sequencing data from lung cancer samples. These mutations were used as predictors to develop a logistic regression machine learning model. The model was tested on sequencing data from a separate set of 578 lung cancer and 545 non-cancer samples from 18 different cohorts. The logistic regression model correctly classified lung cancer and non-cancer blood samples with 94.12% sensitivity (95% Confidence Interval: 92.20-96.04%) and 85.96% specificity (95% Confidence Interval: 82.98-88.95%). Our results suggest that it may be possible to develop an accurate blood-based lung cancer screening panel using this approach. Unlike most other "liquid biopsies" currently under development, the approach presented here is based on standard sequencing protocols and uses a relatively small number of rationally selected mutations as predictors.

Cancer immunotherapy focuses on the use of patients' adaptive immune systems to combat cancer. In the past decade, FDA has approved many immunotherapy products for cancer patients who suffer from primary tumors, tumor relapse, and metastases. However, these immunotherapies still show resistance in many patients and often lead to inconsistent responses in patients due to variations in tumor genetic mutations and tumor immune microenvironment. Microfluidics-based organ-on-a-chip technologies or microphysiological systems have opened new ways that can provide relatively fast screening for personalized immunotherapy and help researchers and clinicians understand tumor-immune interactions in a patient-specific manner. They also have the potential to overcome the limitations of traditional drug screening and testing, given the models provide a more realistic 3D microenvironment with better controllability, reproducibility, and physiological relevance. This review focuses on the cutting-edge microphysiological organ-on-a-chip devices developed in recent years for studying cancer immunity and testing cancer immunotherapeutic agents, as well as some of the largest challenges of translating this technology to clinical applications in immunotherapy and personalized medicine.

Immunotherapy is a promising alternative treatment for canine mast cell tumour (MCT). However, evasion of immune recognition by downregulating major histocompatibility complex (MHC) molecules might decline treatment efficiency. Enhancing MHC expression through interferon-gamma (IFN-γ) is crucial for effective immunotherapy. In-house and reference canine MCT cell lines derived from different tissue origins were used. The impacts of IFN-γ treatment on cell viability, expression levels of MHC molecules, as well as cell apoptosis were evaluated through the MTT assay, RT-qPCR and flow cytometry. The results revealed that IFN-γ treatment significantly influenced the viability of canine MCT cell lines, with varying responses observed among different cell lines. Notably, IFN-γ treatment increased the expression of MHC I and MHC II, potentially enhancing immune recognition and MCT cell clearance. Flow cytometry analysis in PBMCs-mediated cytotoxicity assays showed no significant differences in overall apoptosis between IFN-γ treated and untreated canine MCT cell lines across various target-to-effector ratios. However, a trend towards higher percentages of late and total apoptotic cells was observed in the IFN-γ treated C18 and CMMC cell lines, but not in the VIMC and CoMS cell lines. These results indicate a variable response to IFN-γ treatment among different canine MCT cell lines. In summary, our study suggests IFN-γ's potential therapeutic role in enhancing immune recognition and clearance of MCT cells by upregulating MHC expression and possibly promoting apoptosis, despite variable responses across different cell lines. Further investigations are necessary to elucidate the underlying mechanisms and evaluate IFN-γ's efficacy in in vivo models.

In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.

Cancer represents a significant threat to human health, and traditional chemotherapy or cytotoxic therapy is no longer the sole or preferred approach for managing malignant tumors. With advanced research into the immunogenicity of tumor cells and the growing elderly population, tumor immunotherapy has emerged as a prominent therapeutic option. Its significance in treating elderly cancer patients is increasingly recognized. In this study, we review the conceptual classifications and benefits of immunotherapy, and discuss recent developments in new drugs and clinical progress in cancer treatment through various immunotherapeutic modalities with different mechanisms. Additionally, we explore the impact of immunosenescence on the effectiveness of cancer immunotherapy and propose innovative and effective strategies to rejuvenate senescent T cells.

Metal ions play an essential role in regulating the functions of immune cells by transmitting intracellular and extracellular signals in tumor microenvironment (TME). Among these immune cells, we focused on the impact of metal ions on T cells because they can recognize and kill cancer cells and play an important role in immune-based cancer treatment. Metal ions are often used in nanomedicines for tumor immunotherapy. In this review, we discuss seven metal ions related to anti-tumor immunity, elucidate their roles in immunotherapy, and provide novel insights into tumor immunotherapy and clinical applications.

The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer-related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.

Maturing immunometabolic research empowers immune regulation novel approaches. Progressive metabolic adaptation of tumor cells permits a thriving tumor microenvironment (TME) in which immune cells always lose the initial killing capacity, which remains an unsolved dilemma even with the development of immune checkpoint therapies. In recent years, many studies on tumor immunometabolism have been reported. The development of immunometabolism may facilitate anti-tumor immunotherapy from the recurrent crosstalk between metabolism and immunity. Here, we discuss clinical studies of the core signaling pathways of immunometabolism and their inhibitors or agonists, as well as the specific functions of these pathways in regulating immunity and metabolism, and discuss some of the identified immunometabolic checkpoints. Understanding the comprehensive advances in immunometabolism helps to revise the status quo of cancer treatment. An overview of the new landscape of immunometabolism. The PI3K pathway promotes anabolism and inhibits catabolism. The LKB1 pathway inhibits anabolism and promotes catabolism. Overactivation of PI3K/AKT/mTOR pathway and IDO, IL4I1, ACAT, Sirt2, and MTHFD2 promote immunosuppression of TME formation, as evidenced by increased Treg and decreased T-cell proliferation. The LKBI-AMPK pathway promotes the differentiation of naive T cells to effector T cells and memory T cells and promotes anti-tumor immunity in DCs.

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Over a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and prostate cancers). Higher T regulatory cell proportions were associated with statistically significantly higher lung cancer risk (hazard ratio = 1.22, 95% confidence interval = 1.06-1.41 per percent increase). Increased memory B cell proportions were associated with significantly higher risk of prostate cancer (1.17, 1.04-1.33) and all cancers (1.13, 1.05-1.22). Increased CD8+ naïve cell proportions were associated with significantly lower risk of all cancers in participants ≥55 years (0.91, 0.83-0.98). Other immune cell subtypes did not display statistically significant associations with cancer risk. These results in Black participants align closely with prior findings in largely White populations. Findings from this study could help identify those at high cancer risk and outline risk stratifying to target patients for cancer screening, prevention, and other interventions. Further studies should assess these relationships in other cancer types, better elucidate the interplay of B cells in cancer risk, and identify biomarkers for personalized risk stratification.

Alkaline phosphatase (ALP) is known as one of the most crucial members of the phosphatase family and encompasses the enormous ability to hydrolyze the phosphate group in various biomolecules; by this, it regulates several events in the pool of biological medium. Owing to its overexpression in various cancer cells, recently, its potential has evolved as a prominent biomarker in cancer research. In this article, we have underlined the recent advances (2019 onwards) of alkaline phosphatase in the arena of emerging cancer theranostics. Herein, we mainly focused on phosphate-locked molecular systems such as peptides, prodrugs, and aggregation-induced emission (AIE)-based molecules. When these theranostics encounter cancer cell-overexpressed ALP, it results in the hydrolysis of the phosphate group, which leads to the release of highly cytotoxic agents along with turn-on fluorophore/pre-existing fluorophore.

MRPS24 (Mitochondrial Ribosomal Protein S24) belongs to the mitochondrial ribosomal protein family, which participates in the protein synthesis of the mitochondrion. However, the relationship of MRPS24 with lung adenocarcinoma (LUAD) remained unknown. We aimed to identify its immunological and functional mechanisms in LUAD.

The analysis of MRPS24 expression, clinical features, diagnosis, prognosis, function analysis, genetic alteration, copy number variations, methylation, and tumor microenvironment was investigated by the TCGA, UCSC Xena, GEO, HPA, GEPIA, cBioPortal, MethSurv, TIMER, TIMER2.0, and TISIDB databases.

MRPS24 was found to be more abundant in LUAD tumor tissue than in normal tissue. High levels of MRPS24 expression were found to be an independent prognostic factor by multivariate analysis. Functional analysis revealed that MRPS24 expression was associated with the immune, cell cycle and methylation. MRPS24 methylation level was inversely linked with its expression (p < 0.001). Patients with low MRPS24 methylation had a worse prognosis than those with high methylation (p < 0.05). In addition, the result revealed that the MRPS24 expression was inversely linked to the immune cell infiltration in LUAD. Finally, the validations of the expression level, prognosis, and immune cell infiltration of MRPS24 were in accordance with our previous results.

This study systematically explored that MRPS24 expression was significantly correlated with prognosis, tumorigenesis, genetic alteration, copy number variations, methylation, and immune cell infiltration in LUAD. MRPS24 might be a potential immune-related biomarker in the development and treatment of LUAD, thereby acting as a promising predictor of immunotherapy response in LUAD.

Currently, cancer immunotherapy is widely used as a groundbreaking method that can completely cure advanced cancers. However, this new immunotherapy has the challenge of low patient response, which is often due to many patients' tumors having an immunosuppressive environment, known as cold tumors.

This review aims to introduce various nanomedicine-derived combinational cancer immunotherapy that can transform cold tumor into hot tumors. Initially, we discuss new technologies for combinational immunotherapy based on multifunctional nanomedicines that can deliver combinational immunogenic cell death (ICD) inducers, immune checkpoint blockades (ICBs) and immune modulators (IMs) to targeted tumor tissues at the same time. Ultimately, we highlight how multifunctional nanomedicines for combinational cancer immunotherapy can be used to transform cold tumor into hot tumors against advanced cancers.

Nanomedicine-derived combinational cancer immunotherapy for delivering multiple ICD inducers, ICBs, and IMs at the same time is recognized as a new potential technology that can activate tumor immunity and simultaneously increase the therapeutic efficacy of immune cells that can transform effectively the cold tumors into hot tumors. Finally, nanomedicine-derived combinational cancer immunotherapy can solve the serious problems of low therapeutic efficacy that occurs when treating single drug or simple combinational drugs in cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionary effects on therapeutic strategies for multiple malignancies. Their efficacy depends on their ability to reactivate the host immune system to fight cancer cells. However, adverse reactions to ICIs are common and involve several organs, limiting their use in clinical practice. Although the incidence of cardiovascular toxicity is relatively low, it is associated with serious consequences and high mortality rates. The primary cardiovascular toxicities include myocarditis, pericarditis, Takotsubo syndrome, arrhythmia, vasculitis, acute coronary syndrome, and venous thromboembolism. Currently, the mechanism underlying ICI-associated cardiovascular toxicity remains unclear and underexplored. The diagnosis and monitoring of ICI-associated cardiovascular toxicities mainly include the following indicators: symptoms, signs, laboratory examination, electrocardiography, imaging, and pathology. Treatments are based on the grade of cardiovascular toxicity and mainly include drug withdrawal, corticosteroid therapy, immunosuppressants, and conventional cardiac treatment. This review focuses on the incidence, underlying mechanisms, clinical manifestations, diagnoses, and treatment strategies.

Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.

Primary immune deficiencies (PIDs) are rare genetic disorders characterized by impaired immune function, leading to frequent infections and immune dysregulation. Studies have shown that individuals with PID are at an increased risk of developing malignancies and lymphoproliferative disorders compared with the general population. In this single-center study, we aimed to analyze the occurrence of malignancies and lymphoproliferations in children diagnosed with PID. We retrospectively analyzed the medical records of 550 pediatric patients diagnosed with PIDs at our center. Among them, 17 (3,0%) patients were identified with malignancy and/or benign lymphoproliferation. Eight of the 17 patients (47.0%) had immune dysregulatory diseases, whereas ataxia-telangiectasia was the second most common PID associated with malignancy and/or benign lymphoproliferation (n = 5, 29.4%). Lymphoma was the predominant malignancy (n = 11, 64.7%), and Epstein-Barr virus was identified as the most common viral agent associated with malignancy and/or benign lymphoproliferation in patients with PID (n = 8, 47.0%). Our study highlights the association between PID and malignancies/lymphoproliferations, with immune dysregulation syndromes being the most common subclass associated with malignancies/lymphoproliferations. Early diagnosis, multidisciplinary management, and regular surveillance are crucial in improving patient outcomes and saving lives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.

Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy, highlighting a need for innovative approaches.

We analyzed 658 articles and 87 eligible clinical trials using bibliometric tools and database searches, including annual publication and citation trends, were executed using Web of Science, CiteSpace, and VOS Viewer.

Post-2018, there is a surge in thyroid cancer immunotherapy research, primarily from China and the University of Pisa. Of the 87 trials, 32 were Phase I and 55 were Phase II, mostly exploring combination therapies involving immune checkpoint inhibitors.

The study's dual approach verifies the swift advancement of thyroid cancer immunotherapy from diverse perspectives. Immune checkpoint inhibitors have become the preferred regimen for advanced MTC and ATC in late therapeutic lines. However, since ICB plays a pivotal role in ATC, current clinical trial data show that ATC patients account for more and the curative effect is more accurate. Anticipated future developments are inclined toward combination regimens integrating immunotherapy with chemotherapy or targeted therapies. Emerging approaches, such as bispecific antibodies, cytokine-based therapies, and adoptive cell therapies like CAR-T and TCR-T, are exhibiting considerable potential. Upcoming research is expected to concentrate on refining the tumor immune milieu and discovering novel biomarkers germane to immunotherapeutic interventions.

In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.

We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms.

A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate.

Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage.

Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.