International immunopharmacology · 2026
PA-MSHA promotes antitumor immunity in STK11 mutant NSCLC through activating the STING pathway of immune cells.
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Yin Guofang, He Fang, Guo Qiusha, Jiang Qilan, Fan Shiming, Liu Yue, Fan Xiaoqing, Liang Yuling, Luo Dan, Jin Kaiyu, Wang Zhiguo, Fan Xianming
Аннотация
BACKGROUND: Serine/threonine kinase 11 (STK11) mutant non-small cell lung cancer (NSCLC) exhibits primary resistance to immunotherapy due to a "cold" tumor immune microenvironment (TIME). Therefore, patients with STK11 mutation benefit little from immunotherapy, highlighting the need to explore novel therapeutic strategies for this population.
METHODS: The impact of Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) on immune cells was determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry analysis (FCA). Cell viability assay, colony formation assay, immunofluorescence staining (IF) analysis, western blot, and proteomics were conducted to investigate the antitumor effects and underlying mechanisms.
RESULTS: PA-MSHA enhanced the cytotoxic activity of THP-1 and Jurkat cells against STK11 mutant NSCLC cells in vitro. And in a cell-derived xenograft (CDX) model established with human peripheral blood mononuclear cells (PBMCs), PA-MSHA in combination with sintilimab effectively inhibited tumor growth. Mechanistically, PA-MSHA induced an immune response TIME, reprogrammed immune cell phenotypes and promoted their cytotoxic functions both in vitro and in vivo. Analysis of proteomics found that PA-MSHA could upregulate the stimulator of interferon genes (STING) expression of THP-1 cells, and the activation of STING pathway mediated by PA-MSHA in THP-1 and Jurkat cells was experimentally verified.
CONCLUSION: PA-MSHA improved immune cells function and enhanced their antitumor effects against STK11 mutant NSCLC, which was associated with the activation of the STING pathway.
METHODS: The impact of Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) on immune cells was determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry analysis (FCA). Cell viability assay, colony formation assay, immunofluorescence staining (IF) analysis, western blot, and proteomics were conducted to investigate the antitumor effects and underlying mechanisms.
RESULTS: PA-MSHA enhanced the cytotoxic activity of THP-1 and Jurkat cells against STK11 mutant NSCLC cells in vitro. And in a cell-derived xenograft (CDX) model established with human peripheral blood mononuclear cells (PBMCs), PA-MSHA in combination with sintilimab effectively inhibited tumor growth. Mechanistically, PA-MSHA induced an immune response TIME, reprogrammed immune cell phenotypes and promoted their cytotoxic functions both in vitro and in vivo. Analysis of proteomics found that PA-MSHA could upregulate the stimulator of interferon genes (STING) expression of THP-1 cells, and the activation of STING pathway mediated by PA-MSHA in THP-1 and Jurkat cells was experimentally verified.
CONCLUSION: PA-MSHA improved immune cells function and enhanced their antitumor effects against STK11 mutant NSCLC, which was associated with the activation of the STING pathway.