biostudies-literatureGuo YNational Natural Science Foundation of China3229-3242https://www.ebi.ac.uk/biostudies/studies/S-EPMC10992087biostudies-literatureUnknown72(10)Existing immune checkpoint inhibitors focus on activating T cells and show limited effectiveness in gastric cancer (GC). SIGLEC10 is identified as a novel tumor-associated macrophage-related immune checkpoint in other cancer types. However, its immunosuppressive role and clinical significance in GC remain unclear. In this study, we find a dominant expression of SIGLEC10 on CD68⁺ macrophages in GC. SIGLEC10 can suppress the proliferation and function of tumor-infiltrating CD8⁺ T cells in vitro via the Akt/P38/Erk signaling pathway. Furthermore, in ex vivo and in vivo models, SIGLEC10 blockade promotes CD8⁺ T cell effector function. Finally, SIGLEC10⁺ macrophages are positively correlated with the adverse prognosis of GC. Our study highlights that Cancer immunology, immunotherapy : CIISIGLEC10⁺ macrophages drive gastric cancer progression by suppressing CD8⁺ T cell function.PMC109920873207087881970497Liu XXie FGuo YChen JLu HXu DZhao GZhao WShen YWang ZKe SfalseSIGLEC10⁺ macrophages drive gastric cancer progression by suppressing CD8⁺ T cell function.Existing immune checkpoint inhibitors focus on activating T cells and show limited effectiveness in gastric cancer (GC). SIGLEC10 is identified as a novel tumor-associated macrophage-related immune checkpoint in other cancer types. However, its immunosuppressive role and clinical significance in GC remain unclear. In this study, we find a dominant expression of SIGLEC10 on CD68⁺ macrophages in GC. SIGLEC10 can suppress the proliferation and function of tumor-infiltrating CD8⁺ T cells in vitro via the Akt/P38/Erk signaling pathway. Furthermore, in ex vivo and in vivo models, SIGLEC10 blockade promotes CD8⁺ T cell effector function. Finally, SIGLEC10⁺ macrophages are positively correlated with the adverse prognosis of GC. Our study highlights that 2023-01-01T00:00:00Z2023 Oct2026-04-29T14:06:52.418Z2026-04-07T15:15:16.799ZS-EPMC109920873743240710.1007/s00262-023-03488-2