Combination of Anti-PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable...

Area of Science:

• Immunology
• Oncology
• Integrative Medicine

Background:

• Programmed death receptor-1 (PD-1) inhibitors show limited efficacy in microsatellite-stable (MSS) colorectal cancer.
• Electroacupuncture (EA) possesses known oncosuppressive and immunomodulatory effects.

Purpose of the Study:

• To investigate the antitumor effects of EA in MSS colorectal cancer.
• To explore the potential of combining EA with anti-PD-1 therapy for MSS colorectal cancer.

Main Methods:

• Investigated EA's antitumor effects and optimal intensity in MSS colorectal cancer mouse models.
• Analyzed EA's impact on immune responses, including lymphocyte and granzyme B levels, and the STING pathway.
• Evaluated the efficacy of combined EA and anti-PD-1 therapy using single-cell RNA sequencing to assess tumor immune microenvironment (TIME) reprogramming.

Main Results:

• Moderate-intensity EA (1.0 mA) demonstrated maximal tumor inhibition.
• EA enhanced antitumor immunity by increasing lymphocytes and granzyme B, and activating the STING pathway.
• Combination therapy of EA and anti-PD-1 exhibited superior antitumor efficacy compared to monotherapy, reprogramming the TIME and enhancing cytotoxic functions.

Conclusions:

• EA reshapes the tumor immune microenvironment in MSS colorectal cancer, sensitizing it to anti-PD-1 therapy via the STING pathway.
• EA is a safe, well-tolerated, and clinically feasible immunomodulatory strategy.
• This study provides a mechanistic basis for using EA to improve anti-PD-1 efficacy in MSS colorectal cancer.