ArticleTranslational oncology2024
Collagen extracellular matrix promotes gastric cancer immune evasion by activating IL4I1-AHR signaling.
Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Enzyme-mediated remodeling of the extracellular matrix and glycocalyx to enhance immunotherapy in solid tumors.Bioengineering & translational medicine · 2026Review
- Exploration and experimental verification of triaptosis-related prognostic genes and cells in gastric cancer.Molecular biology reports · 2026Article
- Review
- IL4I1+ macrophages drive hepatocellular carcinoma progression by responding to biomechanical cues.JHEP reports : innovation in hepatology · 2026Article
- Catalytic nanotherapeutics with cancer cell membrane and chitosan-coated Cu/Pt nanoparticles for gastric cancer precision therapy.Journal of biological engineering · 2026Article
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- Immune modulation in gastric cancer: from macrophage polarization to immunotherapy.Frontiers in immunology · 2026Review
- Single-Cell Transcriptome Atlas Reveals the Underlying Mechanism of Kynurenic Acid in the Regulation of Tumor Immune Microenvironment in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial Fibroblast-Macrophage Niches in Gastric Cancer: Mechanisms of Immune Exclusion, Therapeutic Resistance, and Targeted Intervention.OncoTargets and therapy · 2026Review
- Unlocking the potential: current landscape and future directions of immunotherapy in gastric cancer.Frontiers in immunology · 2026Review
- MiR-124-3p inhibits stomach adenocarcinoma progression by targeting AHR to induce autophagy.Cell division · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies.Cell death & disease · 2025Review
- Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.Current oncology (Toronto, Ont.) · 2025Review
- Adoptive immune cell therapy for colorectal cancer.Frontiers in immunology · 2025Review
- Review
- From spheroids to organoids: next-generation models for CAR-T cell therapy research in solid tumors.Frontiers in immunology · 2025Review
- Emerging HER2 Targeting Immunotherapy for Cholangiocarcinoma.Oncology research · 2025Review
- Visualizing the Tumor Microenvironment: Molecular Imaging Probes Target Extracellular Matrix, Vascular Networks, and Immunosuppressive Cells.Pharmaceuticals (Basel, Switzerland) · 2024Review
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3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastric cancer (GC) remains a significant global health challenge with poor prognosis, partly due to its ability to evade the immune system. The extracellular matrix (ECM), particularly collagen, plays a crucial role in tumor immune evasion, but the underlying mechanisms are not fully understood. This study investigates the role of collagen ECM in promoting immune evasion in gastric cancer by activating the IL4I1-AHR signaling pathway.
methodsWe cultured gastric cancer cells in 3D collagen gels and assessed their immune evasion capabilities by co-culturing with HER2-specific CAR-T cells. The expression of IL4I1 and its metabolites was analyzed, and the role of integrin αvβ1 in mediating the effects of collagen was explored. Additionally, the impact of IL4I1-induced AHR activation on CAR-T cell exhaustion was evaluated, both in vitro and in vivo.
resultsWe found that gastric cancer cells cultured on collagen exhibited increased resistance to CAR-T cell cytotoxicity, which was associated with upregulated immune checkpoint molecules and downregulated effector cytokines on CAR-T cells. This was linked to increased IL4I1 expression, which was further induced by integrin αvβ1 signaling within the 3D collagen environment. IL4I1 metabolites, particularly KynA, promoted CAR-T cell exhaustion by activating the AHR pathway, leading to decreased cytotoxicity and tumor growth inhibition.
conclusionsOur study reveals a novel mechanism by which the collagen ECM facilitates immune evasion in gastric cancer through the activation of IL4I1-AHR signaling, contributing to CAR-T cell exhaustion. Targeting this pathway could potentially enhance the efficacy of CAR-T cell therapy in gastric cancer.
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