title: T helper 17 cells promote cytotoxic T cell activation in tumor immunity.
abstract: Although T helper 17 (Th17) cells have been found in tumor tissues, their function in cancer immunity is unclear. We found that interleukin-17A (IL-17A)-deficient mice were more susceptible to developing lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the Th17 cells retained their cytokine signature and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 cells elicited a remarkable activation of tumor-specific CD8(+) T cells, which were necessary for the antitumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and in draining lymph nodes increased CD8 alpha(+) dendritic cells containing tumor material. Moreover, Th17 cells promoted CCL20 chemokine production by tumor tissues, and tumor-bearing CCR6-deficient mice did not respond to Th17 cell therapy. Thus, Th17 cells elicited a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. These findings have important implications in antitumor immunotherapies.
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Orozco
authors.forename: Pawel
authors.initials: P
authors.lastname: Muranski
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
authors.forename: Xuexian O
authors.initials: XO
authors.lastname: Yang
authors.forename: Tomohide
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Sijie
authors.initials: S
authors.lastname: Lu
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Willem W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology*; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17