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Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients. [ABSTRACT FROM AUTHOR]

Objectives: CD4 + T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4 + T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown., Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4 + T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4 + T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity., Results: In comparison with CD4 + T cells from the non-tumor tissues, significantly more GC-infiltrating CD4 + T cells expressed CD39. Most GC-infiltrating CD39 + CD4 + T cells exhibited CD45RA - CCR7 - effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39 - CD4 + counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39 + CD4 + T cells were positively associated with disease progression and patients' poorer overall survival., Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4 + T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Objective: To investigate the regulation effect of α-momordicin (α-MMC) on the synthesis and secretion of cytokines in hepatocytes cells., Methods: Hepatocytes L02 were treated with 189 μg/mL α-MMC with culture supernatant and lysate samples were harvested in different timepoint. Expressions of T-helper 17 (TH17) cytokine profile in samples were detected by the Bio-Plex 200 suspension chip assay system., Results: Compared with 0 h, after the α-MMC treatment of L02 hepatocytes for 2 h, 4 h and 8 h, the intracellular synthesis of cytokines interleukin (IL)-1b, IL-6, IL-17A, IL-31, IL-33, soluble CD40 ligand (sCD40L), tumor necrosis factor-α (TNF-α) were all significantly decreased ( P <0.05), and IL-6, IL-4, IL-17A, and sCD40L secreted into the extracellular fluid also decreased significantly ( P <0.05)., Conclusion: α-MMC can significantly inhibit the synthesis and secretion of cytokines such as IL-6, IL-17A and TNF-α in hepatocytes, which may become a side effect of its anti-tumor application., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)