Siglec-G 通过代谢重编程抑制 CD8(+) T 细胞应答，可作为增强肿瘤免疫治疗的靶点

CD8 + T cells play a critical role in cancer immune-surveillance and pathogen elimination.

However, their effector function can be severely impaired by inhibitory receptors such as programmed death-1 (PD-1) and T cell immunoglobulin domain and mucin domain-3 (Tim-3).

Here Siglec-G is identified as a coinhibitory receptor that limits CD8 + T cell function. Siglec-G is highly expressed on tumor-infiltrating T cells and is enriched in the exhausted T cell subset. Ablation of Siglec-G enhances the efficacy of adoptively transferred T cells and chimeric antigen receptor (CAR) T cells in suppressing solid tumors growth.

Mechanistically, sialoglycan ligands, such as CD24 on tumor cells, activate the Siglec-G-SHP2 axis in CD8 + T cells, impairing metabolic reprogramming from oxidative phosphorylation to glycolysis, which dampens cytotoxic T lymphocyte (CTL) activation, expansion, and cytotoxicity.

These findings discover a critical role for Siglec-G in inhibiting CD8 + T cell responses, suggesting its potential therapeutic effect in adoptive T cell therapy and tumor immunotherapy.