How tumors might withstand γδ T-cell attack

Several clinical trials are currently assessing the therapeutic activity of human TCRV gamma 9V delta 2(+) lymphocytes in cancer. Growing tumors usually follow a triphasic Elimination, Equilibrium, Escape evolution in patients. Thus, at diagnostic, most tumors have already developed some means to escape to immune protection. We review here the conventional immunoescape mechanisms which might also protect against cytolytic TCRV gamma 9V delta 2(+) lymphocytes activated by phosphoantigens. Neutralization of these deleterious processes might prove highly valuable to improve the efficacy of ongoing gamma delta cell-based cancer immunotherapies.