Human Vγ9Vδ2 T cells exert anti-tumor activity independently of PD-L1 expression in tumor cells

Human gamma delta T cells expressing V gamma 9V delta 2 T cell receptors play a crucial role in the innate immune system and have an attracted interest as effector cells in adoptive cellular immunotherapy. However, the efficacy of adoptive cellular immunotherapy for the treatment of tumors requires overcoming the immunosuppressive microenvironment. alpha beta T cell inhibition in the tumor microenvironment is associated with programmed death-ligand 1 (PD-L1) expression level. V gamma 9V delta 2 T cells (abbreviated as gamma delta T cells here) exert potent cytotoxic effects in various cancers; however, gamma delta T cell activity in relation to the level of PD L1 expression in cancer cells remains unclear, and the association between the PD-1/PD-L1 axis and gamma delta T cell cytotoxicity needs to be investigated. In this study, PD-1 blockade did not increase the cytotoxicity of gamma delta T cells against PD-L1(high) cancer cells. However, the anti-PD-L1 monoclonal antibody (mAb) enhanced the cytotoxicity of gamma delta T cells against a subset of cancer cells, whereas PD-L1 knockdown did not increase the cytotoxicity of gamma delta T cells. We also found that the expression levels of PD-L1 were positively correlated with the changes of gamma delta T cells cytotoxicity induced by anti-PD-L1 mAb. These observations suggest that anti-PD-L1 mAb treatment adds ADCC activity to the cytotoxicity of gamma delta T cells itself against PD-L1(high) cancer cells. The present results suggest that ex vivo expanded gd T cells have antitumor activity independently of PD-L1 expression and may be promising effector cells for gamma delta T cell immunotherapy. (C) 2021 The Authors. Published by Elsevier Inc.

Automated summary

The study found that PD-1 blockade did not enhance the cytotoxicity of gamma delta T cells against PD-L1(high) cancer cells, but the anti-PD-L1 monoclonal antibody showed an increase in cytotoxicity. PD-L1 knockdown did not affect gamma delta T cell cytotoxicity. The findings suggest that anti-PD-L1 mAb treatment can enhance the cytotoxicity of gamma delta T cells against PD-L1(high) cancer cells.