1. Academic Validation
  2. Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression

Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression

  • Cell Commun Signal. 2020 Jul 8;18(1):106. doi: 10.1186/s12964-020-00611-z.
Yingying Gao 1 2 Haoyu Xu 3 Nan Li 3 Hexi Wang 3 Lei Ma 4 Shiyou Chen 3 Jiayu Liu 3 Yongbo Zheng 3 Yao Zhang 5
Affiliations

Affiliations

  • 1 Department of Laboratory Diagnosis, Chongqing Medical University, Chongqing, 408000, China.
  • 2 Department of Laboratory Diagnosis, Jiamusi University, Jiamusi, 154000, Heilongjiang, China.
  • 3 Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1, medical college road, Yuzhong district, Chongqing, 408000, China.
  • 4 Department of Laboratory Diagnosis, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, Heilongjiang, China.
  • 5 Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1, medical college road, Yuzhong district, Chongqing, 408000, China. zhangyao7407@126.com.
Abstract

Backgound: Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear.

Methods: For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs.

Results: This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a Toll Like Receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence.

Conclusion: The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy. Video abstract.

Keywords

Antigen-specificity; HSP70; MDSCs; RDEs; Tumor immune escape.

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