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

• DOI: 10.1007/s00262-023-03488-2
• Publication Date: 2023-07-11T08:02:04Z
• Authors: Yixian Guo; Shouyu Ke; Feng Xie; Jieqiong Chen; Xu Liu; Zeyu Wang; Danhua Xu; Yanying Shen; Gang Zhao; Wenyi Zhao; Hong Lu
• Keywords: Cancer Immunotherapy; Ex vivo; Immune checkpoint

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.