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Gastric cancer-derived exosomal miR-135b-5p impairs the function of Vγ9Vδ2 T cells by targeting specificity protein 1

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Abstract

Recent studies have shown that tumor-derived exosomes participate in the communication between tumor cells and their microenvironment and mediate malignant biological behaviors including immune escape. In this study, we found that gastric cancer (GC) cell-derived exosomes could be effectively uptaken by Vγ9Vδ2 T cells, decrease the cell viability of Vγ9Vδ2 T cells, induce apoptosis, and reduce the production of cytotoxic cytokines IFN-γ and TNF-α. Furthermore, we demonstrated that exosomal miR-135b-5p was delivered into Vγ9Vδ2 T cells. Exosomal miR-135b-5p impaired the function of Vγ9Vδ2 T cells by targeting specificity protein 1 (SP1). More importantly, blocking the SP1 function by Plicamycin, an SP1 inhibitor, abolished the effect of stable miR-135b-5p knockdown GC cell-derived exosomes on Vγ9Vδ2 T cell function. Collectively, our results suggest that GC cell-derived exosomes impair the function of Vγ9Vδ2 T cells via miR-135b-5p/SP1 pathway, and targeting exosomal miR-135b-5p/SP1 axis may improve the efficiency of GC immunotherapy based on Vγ9Vδ2 T cells.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81802843, 82073156, 81672372); Suzhou Science & Technology plan project (SYS2019035, SS2019077).

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Authors and Affiliations

  1. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China

    Juntao Li, Linqing Sun, Jin Shen, Jiayu Wang, Yanzheng Gu, Guangbo Zhang, Tongguo Shi & Weichang Chen

  2. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China

    Juntao Li, Linqing Sun, Yanjun Chen, Jinghan Zhu & Weichang Chen

  3. Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China

    Jiayu Wang, Yanzheng Gu, Guangbo Zhang & Tongguo Shi

  4. Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China

    Yanzheng Gu, Guangbo Zhang & Tongguo Shi

  5. Suzhou Red Cross Blood Center, 355 Shizi Road, Suzhou, China

    Mingyuan Wang

  6. Jiangsu Province, 50 Donghuan Road, Suzhou, 215100, China

    Weichang Chen

  7. Jiangsu Province, 708 Renmin Road, Suzhou, 215100, China

    Tongguo Shi

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Contributions

JL, TS, and WC designed the experiments; JL, LS, YC, and JZ performed most of the experiments; JS, JW, and GZ assisted with experiments and analysis of the data; MW and YG contributed to provide clinical samples; JL, TS, and WC wrote the manuscript.

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Correspondence to Tongguo Shi or Weichang Chen.

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Li, J., Sun, L., Chen, Y. et al. Gastric cancer-derived exosomal miR-135b-5p impairs the function of Vγ9Vδ2 T cells by targeting specificity protein 1. Cancer Immunol Immunother 71, 311–325 (2022). https://doi.org/10.1007/s00262-021-02991-8

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