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Cancer Cell. 2018 Jun 11;33(6):1048-1060.e7. doi: 10.1016/j.ccell.2018.05.004.

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

Author information

1
Department of Microbiology & Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: yolu@wakehealth.edu.
2
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
3
Department of Microbiology & Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
4
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
5
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: yiq@ccf.org.

Abstract

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.

KEYWORDS:

T cell paradigm; adoptive cell therapy; eradication of large advanced tumor; tumor-specific Th9 cells

Comment in

PMID:
29894691
PMCID:
PMC6072282
DOI:
10.1016/j.ccell.2018.05.004
[Indexed for MEDLINE]
Free PMC Article

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