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Supplementary Figure S1 from Combination of Anti–PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable Colorectal Cancer

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posted on 2024-01-03, 08:21 authored by Yuan Wang, Fengyi Liu, Xiaoxue Du, Jiaqi Shi, Rui Yu, Shuang Li, Ruisi Na, Ying Zhao, Meng Zhou, Ying Guo, Liang Cheng, Guangyu Wang, Tongsen Zheng

Supplementary Figure S1 and legend

Funding

National Natural Science Foundation of China (NSFC)

"Tou yan" Action of Heilongjiang province

HMU Marshal Initiative Funding

History

ARTICLE ABSTRACT

Programmed death receptor-1 (PD-1) inhibitors are ineffective against microsatellite-stable (MSS) colorectal cancer. Electroacupuncture (EA) has oncosuppressive and immunomodulatory properties. Here, we investigated the antitumor effects of EA and explored the feasibility of EA combined with anti–PD-1 in MSS colorectal cancer. Results showed that EA exerted its antitumor effect in an intensity-specific manner, and moderate-intensity EA (1.0 mA) induced maximal tumor inhibition. EA enhanced antitumor immune responses by increasing lymphocytes and granzyme B (GzmB) levels, as well as activating the stimulator of IFN genes (STING) pathway. EA combined with anti–PD-1 showed superior efficacy compared with either monotherapy in multiple MSS colorectal cancer 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 that the potentiated effect of EA was dependent upon the STING pathway. Collectively, EA reshapes the TIME of MSS colorectal cancer 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 colorectal cancer. EA is safe, well-tolerated, and feasible for clinical translation as a promising strategy for treating MSS colorectal cancer.