Emerging evidence suggests the importance of basement membrane components in cancer metastasis; however, their specific roles in esophageal carcinoma remain underexplored. To investigate this, we analyzed 152 esophageal cancer and 11 normal esophageal tissue samples, identifying basement membrane-related prognostic signatures through differential gene expression profiling and Least Absolute Shrinkage and Selection Operator regression. A six-gene panel (LAMC2, GPC2, AGRN, ITGA3, LAMA3, and LOXL4) demonstrated robust predictive capacity, which we subsequently integrated with clinical features via nomogram modeling to predict overall survival. Our computational analyses revealed distinct tumor microenvironment immune cell profiles and chemotherapeutic drug sensitivities across risk strata. We performed an immunohistochemical assay to confirm increased tumor tissue expression, thereby reinforcing the clinical relevance of these biomarkers. Experimental validation using KYSE-150 esophageal squamous carcinoma cells demonstrated that while LAMC2 knockdown attenuated cellular migration, AGRN, GPC2, ITGA3, LAMA3, and LOXL4 suppression enhanced migratory capacity. Proliferation assays further revealed increased growth rates upon GPC2, ITGA3, and LAMA3 expression inhibition. Our results established a basement membrane-derived risk model for esophageal carcinoma and revealed the roles of the model genes in tumor progression regulation. This model advances prognostic stratification and provides insights into therapeutic targets.

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. The primary therapies for HCC are liver transplantation, hepatic tumor excision, radiofrequency ablation, and molecular-targeted medicines. An unfavorable prognosis marks HCC and has limited pharmacological response in therapeutic studies. The tumor immune microenvironment (TME) imposes significant selection pressure on HCC, resulting in its evolution and recurrence after various treatments. As the principal cellular constituents of tumor-infiltrating lymphocytes (TILs), T cells have shown both anti-tumor and protumor actions in HCC. T cell-mediated immune responses are pivotal in cancer monitoring and elimination. TILs are recognized for their critical involvement in the progression, prognosis, and immunotherapeutic management of HCC. Foxp3 + , CD8 + , CD3 + , and CD4 + T cells are the extensively researched subtypes of TILs. This article examines the functions and processes of several subtypes of TILs in HCC. Emerging T cell-based therapies, including TILs and chimeric antigen receptor (CAR)-T cell therapy, have shown tumor regression in several clinical and preclinical studies. Herein, it also delves into the existing T cell-based immunotherapies in HCC, with emphasis on TILs and CAR-T cells.

Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts.

To delineate the trends, advancements, and focal points in immunotherapy for GC.

We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2.

There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy.

GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.

Gastric cancer (GC) is considered a highly heterogeneous disease, and currently, a comprehensive approach encompassing molecular data from various biological levels is lacking.

This study conducted different analyses, including the identification of differentially expressed genes (DEGs), weighted correlation networks (WGCNA), single-cell RNA sequencing (scRNA-seq), mRNA expression-based stemness index (mRNAsi), and multiCox analysis, utilizing data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, the machine learning algorithms including least absolute shrinkage and selection operator (LASSO) regression and random forest (RF), combined with multiCox analysis were exploited to identify hub genes. These findings were then validated through the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, and were experimentally confirmed in GC samples by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).

Integrated analysis of TCGA and GEO databases, coupled with LASSO regression and RF algorithms, allowed us to identify 18 hub genes encoding differentially expressed secreted proteins in GC. The results of RT-PCR and bioinformatics analysis revealed four promising biomarkers with optimal diagnostic and prognostic potential. ROC analysis and Kaplan-Meier curves highlighted CHI3L1, FCGBP, VSIG2, and TFF2 as promising biomarkers for GC, offering superior modeling accuracy. These findings were further confirmed by RT-PCR and ELISA, affirming the clinical utility of these four biomarkers. Additionally, CIBERSORT analysis indicated a potential correlation between the four biomarkers and the infiltration of B memory cells and Treg cells.

This study unveiled four promising biomarkers present in the serum of patients with GC, which could serve as powerful indicators of GC and provide valuable insights for further research into GC pathogenesis.

Gastric cancer (GC) is a malignant tumor with poor prognosis. The diverse patterns of programmed cell death (PCD) are significantly associated with the pathogenesis and progression of GC, and it has the potential to serve as prognostic and drug sensitivity indicators for GC.

The sequencing data and clinical characteristics of GC patients were downloaded from The Cancer Genome Atlas and GEO databases. LASSO cox regression method was used to screen feature genes and develop the PCD score (PCDS). Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore immunotherapy response. By integrating PCDS with clinical characteristics, we constructed and validated a nomogram that demonstrated robust predictive performance.

We screened nine PCD-related genes (SERPINE1, PLPPR4, CDO1, MID2, NOX4, DYNC1I1, PDK4, MYB, TUBB2A) to create the PCDS. We found that GC patients with high PCDS experienced significantly poorer prognoses, and PCDS was identified as an independent prognostic factor. Furthermore, there was a significant difference in immune profile between high PCDS and low PCDS groups. Additionally, drug sensitivity analysis indicated that patients with a high PCDS may exhibit resistance to immunotherapy and standard adjuvant chemotherapy regimens; however, they may benefit from the FDA-approved drug Dasatinib.

Overall, we confirmed that the PCDS is a prognostic risk factor and a valuable predictor of immunotherapy response in GC patients, which provides new evidence for the potential application of GC.

Recent studies have highlighted the distinct ratio of PD-1 + Treg/PD-1 + CD8 for prognosis prediction. However, it remains unclear about the association of this ratio and tertiary lymphoid structures (TLS) with prognosis and response to neoadjuvant or conversion therapy in advanced gastric cancer.

Firstly, fresh postoperative samples from 68 gastric cancer patients in Renji Hospital were collected. Meanwhile, immune cell infiltration as well as clinical prognosis analysis were conducted. Subsequently, we further systematically evaluated flow cytometry analysis of tumor samples and TLS expression in 38 gastric cancer patients with different response situations after neoadjuvant therapy. Also, a Renji conversion therapy cohort including 10 patients with complete matching samples before and after treatment was established to receive RNA sequencing analysis and multiplex immunohistochemistry (mIHC) tests. The corresponding TLS score and immune cell infiltration were further compared based on therapeutic response variations.

In general, the ratio of PD-1 + Treg/PD-1 + CD8>1 could be regarded as an independent predictor of prognosis in advanced gastric cancer patients. Moreover, PD-1 + Treg/PD-1 + CD8 < 1 and high expression of TLS could indicate better neoadjuvant therapy response and extended survival time in advanved gastric cancer patients. Besides, PD-1 + Treg/PD-1 + CD8 low &TLS high group could predict better progression free survival time (PFS) in complete response (CR) subgroup. In response group after conversion therapy, the number of PD-1 + CD8 + T cells significantly increased, mainly occurring outside the TLSs. Meanwhile, the TLSs were also considerably activated as we could observed.

This study underlined that combining PD-1 + Treg/PD-1 + CD8 ratio and TLS were significantly associated with prognosis and preoperative treatment response in advanced gastric cancer. Inspiringly, these indicators have the potential to elucidate the immune balance of advanced gastric cancer patients and can accurately guide subsequent therapeutic strategies.

Gastric cancer (GC) presents significant management challenges. MPT-driven necrosis (MPTDN) plays a significant role in various conditions, but its connection with GC is unclear. This study aimed to investigate the predictive significance of MPTDN-related genes (MPTDNRGs) in GC and their effect on the tumor immune microenvironment (TIME).

RNA sequencing data for GC were sourced from TCGA and GEO databases. The mutation profiles and MPTDNRG expression between tumor and normal samples were assessed. Prognostic mRNAs were identified using univariate Cox regression and LASSO regression. GC patients were classified into high- and low-risk groups according to risk scores, followed by survival analysis and evaluation of correlations between MPTDN score and clinicopathological features, functional pathway, TIME, and responses to immunotherapy.

MPTDNRGs exhibited a 64% mutation rate in GC, with 22 showing significant expression differences. Univariate Cox and LASSO regression identified 15 independently prognostic MPTDNRGs. The prognostic risk model stratified patients into two groups, revealing significant differences in overall and disease-free survival. A nomogram incorporating the signature and clinical characteristics showed strong specificity and sensitivity in predicting prognosis. The MPTDN score was significantly associated with clinical characteristics, functional pathways, and TIME. scRNA-seq analysis indicated higher MPTDN-signature expression in CD8 + T cells, malignant cells, and myofibroblasts. TIDE analysis suggested high-risk patients have reduced responses to immunotherapy, while low-risk patients could benefit more. Importantly, validation using urothelial carcinoma data confirmed a better prognosis for low-risk patients with immunotherapy.

This study highlights the importance of MPTDN-related signatures in predicting GC prognosis and guiding therapeutic decisions.

Type 2 diabetes mellitus is a complex metabolic disorder characterized by insulin resistance and, subsequently, decreased insulin secretion. This condition is closely linked to obesity, a major risk factor that boosts the development of chronic systemic inflammation, which, in turn, is recognized for its crucial role in the onset of insulin resistance. Under conditions of obesity, adipose tissue, particularly visceral fat, becomes an active endocrine organ that releases a wide range of pro-inflammatory mediators, including cytokines, chemokines, and adipokines. These mediators, along with cluster of differentiation (CD) markers, contribute to the maintenance of systemic low-grade inflammation, promote cellular signaling and facilitate the infiltration of inflammatory cells into tissues. Emerging studies have indicated the accumulation of a new cell population in the adipose tissue in these conditions, known as myeloid-derived suppressor cells (MDSCs). These cells possess the ability to suppress the immune system, impacting obesity-related chronic inflammation. Given the limited literature addressing the role of MDSCs in the context of type 2 diabetes, this article aims to explore the complex interaction between inflammation, obesity, and MDSC activity. Identifying and understanding the role of these immature cells is essential not only for improving the management of type 2 diabetes but also for the potential development of targeted therapeutic strategies aimed at both glycemic control and the reduction in associated inflammation.

Gastric cancer is one of the most common cancers and is one of the leading causes of cancer-related deaths in worldwide. Early diagnosis and treatment are essential for a positive outcome. The integration of artificial intelligence in the pathology field is increasingly widespread, including histopathological images analysis. In recent years, the application of digital pathology technology emerged as a potential solution to enhance the understanding and management of gastric cancer. Through sophisticated image analysis algorithms, artificial intelligence technologies facilitate the accuracy and sensitivity of gastric cancer diagnosis and treatment and personalized therapeutic strategies. This review aims to evaluate the current landscape and future potential of artificial intelligence in transforming gastric cancer pathology, so as to provide ideas for future research.

The impact of racial healthcare disparities has been well documented. Adverse social determinants of health, such as poverty, inadequate housing, and limited access to healthcare, are intricately linked to these disparities and negative health outcomes, highlighting the profound impact that social and economic factors have on individuals' overall well-being. Recent evidence underscores the role of residential location on individual health outcomes. Despite the importance of a healthy lifestyle, regular physical activity, balanced nutrition, and stress management for favorable health outcomes, individuals living in socioeconomically disadvantaged areas may face obstacles in achieving these practices. Adverse living conditions, environmental factors, and systemic biases against Black Americans perpetuate allostatic load. This, compounded by decreased physical activity and limited healthy food options, may contribute to increased oxidative stress and inflammation, fundamental drivers of morbidities such as cardiovascular disease and cancer. Herein, we perform a narrative review of associations between healthcare disparities, chronic stress, allostatic load, inflammation, and cancer in Black Americans, and we discuss potential mechanisms and solutions. Additional research is warranted in the very important area of cancer disparities.

Gastric cancer is one of the most common malignant tumors worldwide, and surgical resection is one of the main ways to treat gastric cancer. However, the immune status of postoperative patients is crucial for prognosis and survival, and immune cells play an important role in this process. Therefore, it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells, especially total T cells (CD3+), helper T cells (CD3+CD4+), and suppressor T cells (CD3+CD8+), and its relationship to survival.

To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery, detect the levels of total T cells, helper T cells and suppressor T cells.

A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study. Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells, helper T cells and inhibitory T cells. To explore the relationship between these immune markers and patient survival.

The results showed that the levels of total T cells, helper T cells, and suppressor T cells changed in patients after gastric cancer surgery. There was a significant positive correlation between total T cells, helper T cells and suppressor T cells (r = 0.35, P < 0.01; r = 0.56, P < 0.01). However, there was a negative correlation between helper T cells and suppressor T cells (r = -0.63, P < 0.01). Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group (28.87 ± 24.98 months vs 18.42 ± 16.21 months). The survival curve shows that the curve of patients in the high-level group is shifted to the upper right, and that of the low-level group is shifted downward. There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time.

By detecting peripheral blood immune cells with flow cytometry, we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.

Melanoma is a malignant skin tumor with a high mortality rate. Regulatory T cells (Tregs) are immune cells with immunosuppressive roles, however, the precise mechanisms governing Treg involvement in melanoma remain enigmatic. Experimental findings unveiled different transcription factor switches between normal and tumor T cell, with heightened FOXP3 and BATF in the latter. These factors induced immunosuppressive molecules and Treg maintenance genes, polarizing tumor T cells into Tregs. Spatial transcriptomics illuminated the preferential settlement of Tregs at the melanoma periphery. Within this context, FOXP3 in Tregs facilitated direct enhancement of specific ligand gene expression, fostering communication with neighboring cells. Novel functional molecules bound to FOXP3 or BATF in Tregs, such as SPOCK2, SH2D2A, and ligand molecules ITGB2, LTA, CLEC2C, CLEC2D, were discovered, which had not been previously reported in melanoma Treg studies. Furthermore, we validated our findings in a large number of clinical samples and identified the Melanoma Treg-Specific Regulatory Tag Set (Mel TregS). ELISA analysis showed that the protein levels of Mel TregS in melanoma Tregs were higher than in normal Tregs. We then utilized SERS technology to measure the signal values of Mel TregS in exosome, and successfully discriminated between healthy individuals and melanoma patients, as well as early and late-stage patients. This approach significantly enhanced detection sensitivity. In sum, our research elucidated fresh insights into the mechanisms governing Treg self-maintenance and communication with surrounding cells in melanoma. We also introduced an innovative method for clinical disease monitoring through SERS technology.

The occurrence of ovarian cancer (OC) is a major factor in women's mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.

Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated.

MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor.

The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 μg. Antares2-MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo.

S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, and lipids and can serve as messengers for intercellular communication. They play critical roles in the exchange of information between tumor cells and the tumor microenvironment (TME). The TME consists of mesenchymal cells and components of the extracellular matrix (ECM), with fibroblasts being the most abundant cell type in the tumor mesenchyme. Cancer-associated fibroblasts (CAFs) are derived from normal fibroblasts and mesenchymal stem cells that are activated in the TME. CAFs can secrete exosomes to modulate cell proliferation, invasion, migration, drug resistance, and other biological processes in tumors. Additionally, tumor cells can manipulate the function and behavior of fibroblasts through direct cell-cell interactions. This review provides a summary of the intercellular crosstalk between GI tumor cells and CAFs through exosomes, along with potential underlying mechanisms.

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.

Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health.

CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines.

In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer.

The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration.

These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.