程序性死亡受体 1 (PD-1) 抑制剂对微卫星稳定 (MSS) 结直肠癌 (CRC) 无效。电针（EA）具有肿瘤抑制和免疫调节特性。在这里，我们研究了 EA 的抗肿瘤作用，并探讨了 EA 联合抗 PD-1 在 MSS CRC 中的可行性。结果表明，电针以强度特异性方式发挥抗肿瘤作用，中等强度的电针（1.0 mA）可诱导最大程度的肿瘤抑制。 EA 通过增加淋巴细胞和颗粒酶 B (GzmB) 水平以及激活干扰素基因刺激剂 (STING) 途径来增强抗肿瘤免疫反应。在多个 MSS CRC 小鼠模型中，EA 联合抗 PD-1 药物显示出比任一单一疗法更优越的疗效。单细胞 RNA 测序表明，共治疗重新编程了肿瘤免疫微环境 (TIME)，其特点是细胞毒功能增强。从机制上讲，我们发现 EA 的增强作用依赖于 STING 通路。总的来说，EA 重塑了 MSS CRC 的时间，并以 STING 通路依赖性方式使肿瘤对抗 PD-1 敏感。这些结果为使用 EA 作为免疫调节策略来提高抗 PD-1 在 MSS CRC 中的临床疗效提供了机制原理。 EA 安全、耐受性良好且可用于临床转化，作为治疗 MSS CRC 的有前途的策略。

Programmed death receptor-1 (PD-1) inhibitors are ineffective against microsatellite-stable (MSS) colorectal cancer (CRC). Electroacupuncture (EA) has onco-suppressive and immunomodulatory properties. Here, we investigated the anti-tumor effects of EA and explored the feasibility of EA combined with anti-PD-1 in MSS CRC. Results showed that EA exerted its anti-tumor effect in an intensity-specific manner, and moderate-intensity EA (1.0 mA) induced maximal tumor inhibition. EA enhanced anti-tumor immune responses by increasing lymphocytes and granzyme B (GzmB) levels, as well as activating the stimulator of interferon genes (STING) pathway. EA combined with anti-PD-1 showed superior efficacy compared with either monotherapy in multiple MSS CRC mouse models. Single-cell RNA sequencing revealed that cotreatment reprogrammed the tumor immune microenvironment (TIME), as characterized by enhancement of cytotoxic functions. Mechanically, we found the potentiated effect of EA was dependent upon the STING pathway. Collectively, EA reshapes the TIME of MSS CRC and sensitizes tumors to anti-PD-1 in a STING pathway-dependent manner. These results provide a mechanistic rationale for using EA as an immunomodulatory strategy to improve the clinical efficacy of anti-PD-1 in MSS CRC. EA is safe, well-tolerated, and feasible for clinical translation as a promising strategy for treating MSS CRC.