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

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

  • Cancer Immunol Immunother. 2022 Feb;71(2):311-325. doi: 10.1007/s00262-021-02991-8.
Juntao Li 1 2,  Linqing Sun 1 2,  Yanjun Chen 2,  Jinghan Zhu 2,  Jin Shen 1,  Jiayu Wang 1 3,  Yanzheng Gu 1 3 4,  Guangbo Zhang 1 3 4,  Mingyuan Wang 5,  Tongguo Shi 6 7 8 9,  Weichang Chen 10 11 12
Affiliations

Affiliations

  • 1 Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China.
  • 3 Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China.
  • 4 Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China.
  • 5 Suzhou Red Cross Blood Center, 355 Shizi Road, Suzhou, China.
  • 6 Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China. shitg@suda.edu.cn.
  • 7 Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, China. shitg@suda.edu.cn.
  • 8 Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China. shitg@suda.edu.cn.
  • 9 Jiangsu Province, 708 Renmin Road, Suzhou, 215100, China. shitg@suda.edu.cn.
  • 10 Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 708 Renmin Road, Suzhou, China. weichangchen@126.com.
  • 11 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, China. weichangchen@126.com.
  • 12 Jiangsu Province, 50 Donghuan Road, Suzhou, 215100, China. weichangchen@126.com.
PMID: 34159436 DOI: 10.1007/s00262-021-02991-8
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.

Keywords

Exosome; Gastric cancer; SP1; Vγ9Vδ2 T cell; miR-135b-5p.

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