The expansion of MDSCs induced by exosomal PD-L1 promotes the progression of gastric cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 3, 2024

Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, molecular process underlying expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. The levels exosomal and soluble PD-L1 ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate correlation between MDSCs, percentage peripheral blood 57 was assessed flow cytometry. Through ultracentrifugation, separated from cell supernatant detected Western blotting, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM). function evaluated immunofluorescence, blotting cytometry a cell-derived xenograft (CDX) model. overall survival (OS) high group significantly lower than that low (P = 0.0042); however, there no significant OS 0.0501). Furthermore, we found expression positively correlated with proportions polymorphonuclear (PMN-MDSCs, r 0.4944, P < 0.001) monocytic (M-MDSCs, 0.3663, 0.005) patients, indicating might induce suppression promoting aggregation MDSCs. In addition, stimulate MDSC proliferation triggering IL-6/STAT3 signaling pathway vitro. CDX model confirmed could tumor development amplification. Exosomal has potential become diagnostic biomarker for patients. Mechanistically, can be activated through provide new strategy against use as treatment target.

Language: Английский

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Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1089 - 1089

Published: Jan. 27, 2025

Advanced gastric cancer (AGC) is characterized by poor prognosis and limited responsiveness to immunotherapy. Tumor-associated macrophages (TAMs) play a pivotal role in progression therapeutic outcomes. In this study, we developed novel gene signature associated with M1-like TAMs using data from the Gene Expression Omnibus (GEO) The Cancer Genome Atlas (TCGA) predict immunotherapy response. This was determined as an independent prognostic indicator for AGC, high-risk patients exhibiting immunosuppressive tumor immune microenvironment (TIME) poorer survival Furthermore, Interferon regulatory factor 8 (IRF8) identified key validated through vitro vivo experiments. IRF8 overexpression reshaped suppressive TIME, leading increased presence of TAMs, IFN-γ+ CD8+ T cells, Granzyme B+ cells. Notably, combination anti-PD-1 therapy significantly inhibited growth syngeneic mouse models. AGC elevated expression were found be more responsive treatment. These findings highlight potential biomarkers evaluation offering insights that could guide personalized treatment strategies.

Language: Английский

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Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 28, 2025

Human epidermal growth factor receptor 2 (HER2) is a critical biomarker and therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancers, despite the initial success of HER2-targeted therapies, such as trastuzumab, resistance to these drugs has emerged major impediment effective long-term treatment. This review examines mechanisms drug HER2-positive G/GEJ cancer, primary explored include alterations HER2 itself, mutations changes expression levels, well downstream signaling pathways, interactions with tumor microenvironment (TME). Furthermore, discusses Novel approaches, including use antibody-drug conjugates (ADCs) combination therapies are assessed for their potential enhance outcomes. By integrating recent research findings clinical trials, this aims provide oncologists researchers insights into developing more treatments patients drug-resistant cancer.

Language: Английский

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A Single-Cell Approach to Analyzing Vascular Endothelial Cell Contributions in VEGF-Driven Angiogenesis and LINC02313 in Gastric Cancer

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 115, P. 108361 - 108361

Published: Jan. 30, 2025

Language: Английский

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Gastric biopsy-derived cell line and its utility in assessing tumor cell drug sensitivity

Biomedical Research, Journal Year: 2025, Volume and Issue: 46(1), P. 27 - 35

Published: Jan. 30, 2025

Gastric cancer (GC) has benefited from treatment improvements such as minimally invasive surgery, molecular-targeted drugs, and immune check point inhibitors. However, the prognosis of advanced GC is still unfavorable. Minimally pre-treatment detection drug sensitivity (MI-PDDS) increasing importance in view improved chemotherapy. biopsy specimens are obtained with relative ease but have not been considered an appropriate source for generating cell lines because their minute amounts. We therefore materialized idea MI-PDDS using biopsy-derived endoscopic specimens. Here, a line designated TCC-GC1-C1 was established specimen histologically confirmed adenocarcinoma stomach. The showed ability forming spheroid deeply stained nuclei disturbed cellular morphology indicative malignancy. Single-nucleotide polymorphism (SNP) genotyping revealed duplication chromosome19q deletion chromosome 8p. A screening test 221 anticancer drugs that had high to proteasome inhibitor (Carfilzomib) fibroblast growth factor receptor (Erdafitinib), low IC50 value under 0.1 μM. Our approach holds promise making decision GC.

Language: Английский

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BTK inhibitors are a possible emerging therapeutic target for gastric cancer

Deleted Journal, Journal Year: 2025, Volume and Issue: 33(1), P. 200935 - 200935

Published: Feb. 3, 2025

Language: Английский

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Research and analysis of circulating tumor cell detection in the diagnosis and treatment of gastric cancer

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(3)

Published: Feb. 13, 2025

BACKGROUND Circulating tumor cells (CTCs) are crucial for improving our knowledge regarding progress, prognosis, and recurrence possibility. AIM To evaluate the role of CTCs in early diagnosis treatment gastric cancer. METHODS From June 2020 to December 2021, a randomized study was conducted institution involving 80 patients scheduled surgery The were divided into two groups: A control group that tested traditional serum markers assessed CTCs. RESULTS In cohort, CTC levels did not correlate significantly with patient age, gender, or degree differentiation (P > 0.05). However, there significant correlation tumor-node-metastasis stage < group, diagnostic positivity rate 62.50% (25 out 40 patients), while conventional 47.50% (19 patients). positive detection higher than CONCLUSION have slight invasion high sensitivity specificity, presenting great value clinical metastasis. It will improve deceleration disease development increase survival rate.

Language: Английский

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The enigma of maladaptation in gastric pathophysiology

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Despite a decline in global incidence, gastric cancer (GC) remains major health concern. The development of GC is sequential, multistage maladaptive process involving numerous different factors. Understanding the complexity crucial for early detection, effective treatment, and, ultimately, prevention. In this respect, identifying impact risk factors contributing to emergence or progression GC, such as Helicobacter pylori infection, host and bacterial genetics, alcohol consumption, smoking, preserved foods, will aid combatting disease. review, we focus on recent developments understanding role microbiome, dysfunctional molecular pathways, immune evasion pathophysiology. We also highlight challenges advances treatment GC.

Language: Английский

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Biological Activity of Peptide Fraction Derived from Hermetia illucens L. (Diptera: Stratiomyidae) Larvae Haemolymph on Gastric Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1885 - 1885

Published: Feb. 22, 2025

Gastric cancer (GC) is one of the leading causes cancer-related mortality worldwide, characterised by poor prognosis and limited responsiveness to chemotherapy. There a need for new more effective anticancer agents. Antimicrobial peptides (AMPs) represent promising class biomolecules this purpose. Naturally occurring in innate immune system, these can also exert cytotoxic effects against cells, earning them designation "anticancer peptides" (ACPs). They have potential be viable support current chemotherapy schedules due their selectivity cells minor propensity induce chemoresistance cells. Insects are an excellent source AMPs. Among them, its ability thrive hostile microorganism-rich environments, we isolated peptide fraction from Hermetia illucens L. (Diptera: Stratiomyidae) haemolymph evaluate possible activity. We tested Peptide Fractions (PFs) AGS KATO III gastric cell lines. Data obtained indicated that PFs, especially those resulting Escherichia coli Micrococcus flavus infection (to boost response), were able inhibit tumour growth inducing apoptosis or cycle arrest line-specific manner. These results further investigation into use antimicrobial produced insects as

Language: Английский

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A Novel Prognostic Marker Based on Metabolic Gene for Gastric Cancer Patients Receiving Immunotherapy

Published: Jan. 1, 2025

Language: Английский

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