Th17 cells promote cytotoxic T cell activation in tumor immunity
By Natalia Martín‐Orozco, P. Muranski, Yeonseok Chung, Xuexian O. Yang, Tomohide Yamazaki, Sijie Lu, P. Hwu, N. Restifo, W. Overwijk, C. Dong. Immunity, 2009
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Summary Although T helper 17 (Th17) cells have been found in human tumor tissues, their function in cancer immunity is unclear. Here we show that IL-17-deficient mice were more susceptible to the development of lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the donor Th17 cells retained their cytokine expression phenotype and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 but not Th1 cells elicited a remarkable activation of tumor-specific CD8+ T cells, which were necessary for the anti-tumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and greatly increased the numbers of CD8α+ dendritic cells containing tumor materials in draining lymph nodes. Moreover, compared to Th1 cells, Th17 cells promoted CCL20 chemokine production in tumor tissues and tumor-bearing CCR6-deficient mice were completely impaired in responding to Th17 therapy. Our data indicate that Th17 cells elicit a protective inflammation that ultimately promotes the activation of tumor-specific CD8+ T cells. These findings have important implications in anti-tumor immunotherapies.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/27dd617f33d5b5b048510f0788a84634ec5102a2
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Citations in the corpus
- Immunity, Inflammation, and Cancer (2010, background): “According to the immunosurveillance hypothesis, NK cells and CTLs engage in tumor killing (via perforin, granzyme B, TRAIL, or FasL-dependent mechanisms), whereas Th1 (by virtue of IFNg production) and in some instances Th17 cells (via production of IL-17A) provide important help that boosts cytotox”