How tumors might withstand γδ T-cell attack

Several clinical trials are currently assessing the therapeutic activity of human TCRVγ9Vδ2⁺ 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 TCRVγ9Vδ2⁺ lymphocytes activated by phosphoantigens. Neutralization of these deleterious processes might prove highly valuable to improve the efficacy of ongoing γδ cell-based cancer immunotherapies.