SIGLEC10+ macrophages drive gastric cancer progression by suppressing CD8+ T cell function

Abstract

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 SIGLEC10 directly suppresses T cell function and serves as a promising target for immunotherapy and suggests SIGLEC10⁺ macrophages as a novel potential predictor of the clinical prognosis of GC.

Keywords: CD68; CD8+ T cell; Gastric cancer; Macrophage; SIGLEC10.