CD137 Costimulation Enhances the Antitumor Activity of Vγ9Vδ2-T Cells in IL-10-Mediated Immunosuppressive Tumor Microenvironment

• DOI: 10.3389/fimmu.2022.872122
• Publication Date: 2022-06-17T04:36:07Z
• Authors: Yujun Pei; Zheng Xiang; Kun Wen; Chloe Ran Tu; Xiwei Wang; Yanmei Zhang; Xiaofeng Mu; Yinping Liu; Wenwei Tu
• Keywords: CD137; Cancer Immunotherapy

Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost cell immunity has shown success in some cancer patients, the clinical application is limited due rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from and profoundly immunosuppressive microenvironment (TME). In this study, a culture medium containing human viral interleukin-10 (hIL-10 vIL-10) secreted EBV-transformed lymphoblastoid B lines (EBV-LCL) mimic TEM, we found that antitumor activity was highly suppressed endogenous hIL-10 vIL-10 within TME. CD137 costimulation could provide an anti-exhaustion signal mitigate suppressive effects IL-10 TME suppressing IL-10R1 expression on cells. also improved compromised with high levels Rag2 -/- γc mice. humanized mice, boosted therapeutic aminobisphosphonate pamidronate against EBV-induced lymphoma. Our study offers novel approach overcoming obstacle vIL-10-mediated costimulating enhancing efficacy therapy.