T helper 17 cells promote cytotoxic T cell activation in tumor immunity.
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.
Martin-Orozco
Natalia
N
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Muranski
Pawel
P
Chung
Yeonseok
Y
Yang
Xuexian O
XO
Yamazaki
Tomohide
T
Lu
Sijie
S
Hwu
Patrick
P
Restifo
Nicholas P
NP
Overwijk
Willem W
WW
Dong
Chen
C
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*
D020381:Interleukin-17