SIGLEC10 巨噬细胞通过抑制 CD8 T 细胞功能促进胃癌进展。

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

机构信息

GI Division, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200025, China.

Department of Gastrointestinal Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200025, China.

出版信息

Cancer Immunol Immunother. 2023 Oct;72(10):3229-3242. doi: 10.1007/s00262-023-03488-2. Epub 2023 Jul 11.

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.

摘要

现有的免疫检查点抑制剂主要针对激活 T 细胞,在胃癌(GC)中的疗效有限。SIGLEC10 在其他癌症类型中被鉴定为一种新型的肿瘤相关巨噬细胞相关免疫检查点。然而,其在 GC 中的免疫抑制作用及其临床意义尚不清楚。在本研究中,我们发现 SIGLEC10 在 GC 中的 CD68 巨噬细胞上呈优势表达。SIGLEC10 可以通过 Akt/P38/Erk 信号通路抑制肿瘤浸润性 CD8 T 细胞的增殖和功能。此外,在离体和体内模型中,SIGLEC10 阻断促进 CD8 T 细胞效应功能。最后,SIGLEC10 巨噬细胞与 GC 的不良预后呈正相关。我们的研究强调,SIGLEC10 直接抑制 T 细胞功能,是免疫治疗的一个有前途的靶点,并提示 SIGLEC10 巨噬细胞是 GC 临床预后的一个新的潜在预测因子。

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