1. SIGLEC10+ macrophages drive gastric cancer progression by suppressing CD8+ T cell function.
- Author
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Guo, Yixian, Ke, Shouyu, Xie, Feng, Chen, Jieqiong, Liu, Xu, Wang, Zeyu, Xu, Danhua, Shen, Yanying, Zhao, Gang, Zhao, Wenyi, and Lu, Hong
- Subjects
CELL physiology ,T cells ,STOMACH cancer ,CANCER invasiveness ,IMMUNE checkpoint inhibitors - 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. [ABSTRACT FROM AUTHOR]- Published
- 2023
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