The tumor microenvironment (TME) in gastric cancer (GC) has been shown to be important for tumor control but the specific characteristics for GC are not fully appreciated. We generated an atlas of 166,533 cells from 10 GC patients with matched paratumor tissues and blood. Our results show tumor-associated stromal cells (TASCs) have upregulated activity of Wnt signaling and angiogenesis, and are negatively correlated with survival. Tumor-associated macrophages and LAMP3⁺ DCs are involved in mediating T cell activity and form intercellular interaction hubs with TASCs. Clonotype and trajectory analysis demonstrates that Tc17 (IL-17⁺CD8⁺ T cells) originate from tissue-resident memory T cells and can subsequently differentiate into exhausted T cells, suggesting an alternative pathway for T cell exhaustion. Our results indicate that IL17⁺ cells may promote tumor progression through IL17, IL22, and IL26 signaling, highlighting the possibility of targeting IL17⁺ cells and associated signaling pathways as a therapeutic strategy to treat GC.

胃癌 (GC) 中的肿瘤微环境 (TME) 已被证明对肿瘤控制很重要，但 GC 的具体特征尚未得到充分认识。我们从 10 名具有匹配的肿瘤旁组织和血液的 GC 患者中生成了 166,533 个细胞的图谱。我们的研究结果表明，肿瘤相关基质细胞 (TASC) 的 Wnt 信号传导和血管生成活性上调，并且与存活率呈负相关。肿瘤相关巨噬细胞和LAMP3 ⁺ DC 参与介导 T 细胞活性并与 TASC 形成细胞间相互作用中枢。克隆型和轨迹分析表明 Tc17 ( IL-17 ⁺ CD8 ⁺T 细胞）起源于组织驻留的记忆 T 细胞，随后可以分化为衰竭的 T 细胞，这表明 T 细胞衰竭的替代途径。我们的结果表明，IL17 ⁺细胞可能通过IL17、IL22和IL26信号传导促进肿瘤进展，突出了靶向IL17 ⁺细胞和相关信号通路作为治疗 GC 的治疗策略的可能性。