ArticlePharmaceuticals (Basel, Switzerland)2024
Cancer Cell Secreted Legumain Promotes Gastric Cancer Resistance to Anti-PD-1 Immunotherapy by Enhancing Macrophage M2 Polarization.
Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Targeting the SELP/PSGL1 axis reprograms M2 macrophages and enhances anti-PD-1 efficacy in gastric cancer.Oncogene · 2026Article
- Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- VCAN promotes the progression and recurrence of esophageal squamous cell carcinoma by remodeling the tumor microenvironment.Scientific reports · 2026Article
- M2-polarized tumor-associated macrophages as key orchestrators of gastric cancer pathogenesis and therapeutic resistance.Discover oncology · 2026Review
- Modulating tumor-associated macrophages through APP-CD74 blockade with IL4R-exosomes synergizes with PD-1 inhibition in gastric cancer.NPJ precision oncology · 2026Article
- LGMNFrontiers in immunology · 2026Article
- LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.Frontiers in immunology · 2026Article
- Protease regulation of tumor-immune cell symbiosis.Trends in cancer · 2025Review
- Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies.Cell death & disease · 2025Review
- Gastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Dual function antibody targeting αvβ3 and PD-L1 provide a promising strategy for solid tumor therapy.Frontiers in immunology · 2025Article
- Targeting tumor-associated macrophages in gastric cancer progression and therapy: insights from molecular mechanisms to therapeutic applications.Frontiers in pharmacology · 2025Review
- Effects of FAPCancer drug resistance (Alhambra, Calif.) · 2025Article
- Recent progress in the study of exosomes in the gastric cancer immune microenvironment.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvβ3, then activate Integrin αvβ3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvβ3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvβ3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.