Pitfalls on the roadmap to gammadelta T cell-based cancer immunotherapies

Human TCRVgamma9Vdelta2+ gammadelta cells are unconventional T lymphocytes which had not been specifically mobilized in any cancer vaccine or immunotherapy so far, although they present the major advantage of mediating an HLA-unrestricted highly cytotoxic activity directed against most human tumor cell types. The rapid development of highly selective small molecule agonists targeting these lymphocytes has recently paved the way to clinical trials assessing their activity against cancer. Despite the serious hopes borne by these new weapons however, many pathways usually enable tumor cells to escape conventional immune responses. Here this minireview discusses how cancer immunoevasion pathways might be relevant to counteract the therapeutic bioactivity of TCRVgamma9Vdelta2+ gammadelta cells.