Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies

Copyright © 2019, Springer Nature Limited
Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.
Funding for this study was provided by grants ZonMW 43400003, VIDI-ZonMW 917.11.337, KWF UU 2013-6426, UU 2014-6790, UU 2015-7601, UU2018-11979 and GADETA to J.K.; UU2017-11393 to Z.S. and J.K.; European Research Council grant CoG_646701 to B.S.S.; and DFG grant FOR 2799-PR727/11-1 to I.P.; as well as by Ligue Contre le Cancer (Equipe labellisée 2017) and SIRIC BRIO grants to J.D.M.