Xiaowei Song

Chinese Academy of Medical Sciences & Peking Union Medical College

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Chunyang Xiong

Peking University

Donglin Yu

Binzhou University

Sun Weihao

Changhai Hospital

Qianyi Yang

Brandeis University

Junbo Liang

Chinese Academy of Medical Sciences & Peking Union Medical College

Xinyuan Cao

Peking Union Medical College Hospital

Yuying Liu

Xuzhou Medical College

Kailong Li

Affiliated Hospital of Jining Medical University

Ruiyang Pang

Chinese Academy of Medical Sciences & Peking Union Medical College

Ning Zhang

Heilongjiang University of Chinese Medicine

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Chinese Academy of Medical Sciences & Peking Union Medical College

Peking University

Peking Union Medical College Hospital

University of Chinese Academy of Sciences

Zhejiang Lab

State Key Laboratory of Turbulence and Complex Systems

Chinese Academy of Sciences

Tsinghua University

Guangzhou Medical University

Sun Yat-sen University

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Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors

Science Advances (2024)

Yingyun Yang Dahan Wen Feng Lin Xiaowei Song Ruiyang Pang

Increasing evidence highlights the importance of immune mechanoregulation in establishing and sustaining tumor-specific cytotoxicity required for desirable immunotherapeutic outcomes. However, the molecular connections between mechanobiological inputs and outputs and the designated immune activities remain largely unclear. Here, we show that partial inhibition of non-muscle myosin II (NM II) augmented the traction force exerted by T cells and potentiated T cell cytotoxicity against tumors. By using T cells from mice and patients with cancer, we found that NM II is required for the activity of NKX3-2 in maintaining the expression of ADGRB3, which shapes the filamentous actin (F-actin) organization and ultimately attributes to the reduced traction force of T cells in the tumor microenvironment. In animal models, suppressing the NM II-NKX3-2-ADGRB3 pathway in T cells effectively suppressed tumor growth and improved the efficacy of the checkpoint-specific immunotherapy. Overall, this work provides insights into the biomechanical regulation of T cell cytotoxicity that can be exploited to optimize clinical immunotherapies.

10.1126/sciadv.adp0631

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