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: Natalia Martin-Orozco, Pawel Muranski, Yeonseok Chung, Xuexian O Yang, Tomohide Yamazaki, Sijie Lu, Patrick Hwu, Nicholas P Restifo, Willem W Overwijk, Chen Dong
• Journal: Immunity (Immunity) Vol. 31 Issue 5 Pg. 787-98 (Nov 20 2009) ISSN: 1097-4180 [Electronic] United States
• PMID: 19879162 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17

Topics

• Animals
• Cell Line, Tumor
• Interleukin-17 (genetics, metabolism)
• Lung Neoplasms (immunology)
• Lymphocyte Activation
• Melanoma (immunology)
• Mice
• Mice, Knockout
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)