Vaccination with immunotherapeutic Listeria monocytogenes induces IL-17+ γδ T cells in a murine model for HPV associated cancer

Abstract

Interleukin 17 (IL-17) is produced during infection with Listeria monocytogenes and is also an important regulator of tumor development with both pro- and anti-tumorigenic effects. αβ T cells and γδ T cells are among the principle producers of IL-17 in response to infection and other proinflammatory conditions. Listeria-based cancer immunotherapies induce IFNγ directed Th1 dependent tumor regression; however, the role of IL-17 in Listeria based immunotherapy has not been addressed. Therefore, we investigated the ability of attenuated Listeria-based immunotherapy to induce IL-17 producing cells in a model of cervical cancer and the potential impact that these cells have on anti-tumor vaccine efficacy. Here we show that vaccination of tumor bearing mice with Listeria vaccines resulted in elevated levels of intratumoral IL-17 and increased IL-17 production by γδ TCR+ cells, exclusively. IL-17 producing cells were lacking in tumors of γδ T-cell-deficient mice; however, the absence of γδ T cells, including IL-17+ γδ T cells, did not alter tumor progression or abrogate the efficacy of the Listeria-based vaccine indicating that αβ T cells are key for clearance of the tumor. Th1 responses, known to be responsible for anti-tumor Listeria-based vaccine efficacy, appear to be sufficient for tumor regression in γδ T-cell-deficient mice. We conclude that the efficacy of Listeria-based vaccine does not rely on γδ T cells (or IL-17 produced by them) in a TC.1 tumor model; however, Listeria-based immunotherapy can be used to induce IL-17+ γδ T cells that are important for regression observed in alternative cancer models.