Contribution of IL-17-producing γδ T cells to the efficacy of anticancer chemotherapy

By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-gamma-producing CD8(+) alpha beta T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17-producing gamma delta (V gamma 4(+) and V gamma 6(+)) T lymphocytes (gamma delta 117 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor delta(-/-) or V gamma 4/6(-/-) mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although gamma delta T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A-IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of gamma delta T cells restored the efficacy of chemotherapy in IL-17A(-/-) hosts. The anticancer effect of infused gamma delta T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4(+) all T cells failed to produce IL-17 after chemotherapy. We conclude that gamma delta 117 cells play a decisive role in chemotherapy-induced anticancer immune responses.