Th9 Cells Represent a Unique Subset of CD4+ T Cells Endowed with the Ability to Eradicate Advanced Tumors

Publication date: 11 June 2018
Source:Cancer Cell, Volume 33, Issue 6
Author(s): Yong Lu, Qiang Wang, Gang Xue, Enguang Bi, Xingzhe Ma, Aibo Wang, Jianfei Qian, Chen Dong, Qing Yi
The antitumor effector T helper 1 (Th1) and Th17 cells represent two T cell paradigms: short-lived cytolytic Th1 cells and "stem cell-like" memory Th17 cells. We report that Th9 cells represent a third paradigm—they are less-exhausted, fully cytolytic, and hyperproliferative. Only tumor-specific Th9 cells completely eradicated advanced tumors, maintained a mature effector cell signature with cytolytic activity as strong as Th1 cells, and persisted as long as Th17 cells in vivo. Th9 cells displayed a unique Pu.1-Traf6-NF-κB activation-driven hyperproliferative feature, suggesting a persistence mechanism rather than an antiapoptotic strategy. Th9 antitumor efficacy depended on interleukin-9 and upregulated expression of Eomes and Traf6. Thus, tumor-specific Th9 cells are a more effective CD4⁺ T cell subset for adoptive cancer therapy.

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Teaser

Lu et al. report that adaptively transferred tumor-specific CD4⁺ Th9 cells eradicate large established murine tumors and protect surviving mice against tumor rechallenge. Th9 cells maintain a mature effector cell signature with cytolytic activity as strong as Th1 cells and persist as long as Th17 cells in vivo.


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