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

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Updated: Feb 9, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

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Yong Lu1, Qiang Wang2, Gang Xue3

  • 1Department 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.

Cancer Cell
|June 13, 2018
PubMed

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 paradigmadoptive cell therapyeradication of large advanced tumortumor-specific Th9 cells

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