Cytokines enhance human Vγ9Vδ2 T cell TCR-dependent and independent effector functions.

Vγ9Vδ2 T cells can recognise various molecules associated with cellular stress or transformation, providing a unique avenue for the treatment of cancers or infectious diseases. Nonetheless, Vγ9Vδ2 T cell-based immunotherapies frequently achieve suboptimal efficacies in vivo. Enhancing the cytotoxic effector function of Vγ9Vδ2 T cells is one potential avenue through which the immunotherapeutic potential of this subset may be improved. We compared the use of four pro-inflammatory cytokines on the effector phenotype and functions of in vitro expanded Vγ9Vδ2 T cells, and demonstrate TCR-independent cytotoxicity mediated through CD26, CD16, and NKG2D which could be further enhanced by IL-23, IL-18, and IL-15 stimulation throughout expansion. This work defines promising culture conditions that could improve Vγ9Vδ2 T cell-based immunotherapies and furthers our understanding of how this subset might recognise and target transformed or infected cells. This article is protected by copyright. All rights reserved.