Th9 cells promote antitumor immune responses in vivo
Yong Lu, … , Jianfei Qian, Qing Yi
Yong Lu, … , Jianfei Qian, Qing Yi
Published October 15, 2012
Citation Information: J Clin Invest. 2012;122(11):4160-4171. https://doi.org/10.1172/JCI65459.
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Research Article

Th9 cells promote antitumor immune responses in vivo

Abstract

Th9 cells are a subset of CD4+ Th cells that produce the pleiotropic cytokine IL-9. IL-9/Th9 can function as both positive and negative regulators of immune response, but the role of IL-9/Th9 in tumor immunity is unknown. We examined the role of IL-9/Th9 in a model of pulmonary melanoma in mice. Lack of IL-9 enhanced tumor growth, while tumor-specific Th9 cell treatment promoted stronger antitumor responses in both prophylactic and therapeutic models. Th9 cells also elicited strong host antitumor CD8+ CTL responses by promoting Ccl20/Ccr6-dependent recruitment of DCs to the tumor tissues. Subsequent tumor antigen delivery to the draining LN resulted in CD8+ T cell priming. In agreement with this model, Ccr6 deficiency abrogated the Th9 cell–mediated antitumor response. Our data suggest a distinct role for tumor-specific Th9 cells in provoking CD8+ CTL-mediated antitumor immunity and indicate that Th9 cell–based cancer immunotherapy may be a promising therapeutic approach.

Authors

Yong Lu, Sungyoul Hong, Haiyan Li, Jungsun Park, Bangxing Hong, Lijuan Wang, Yuhuan Zheng, Zhiqiang Liu, Jingda Xu, Jin He, Jing Yang, Jianfei Qian, Qing Yi

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Figure 7

Th9 cells regulate DC function in a Ccr6-dependent manner.

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Th9 cells regulate DC function in a Ccr6-dependent manner. (A) C57BL/6 m...
(A) C57BL/6 mice (n = 3/group) were i.v. challenged with 1 × 105 B16-OVA-GFP tumor cells and, on the same day, were i.v. transferred with 3 × 106 Th1 or Th9 cells. LLNs were tested using FACS 3 days later for DC populations. Histograms show the percentage of GFP+ DCs gated on CD11c+CD8α+ DCs and CD11c+CD11b+ DCs. (B) Number of total and GFP+ cells for each DC population was calculated from A. Representative results from one of two performed experiments are shown. (C) PBS or 3 × 106 Th9 cells were transferred to mice (wild-type and Ccr6–/– mice; n =4/group) bearing 5-day established pulmonary B16-OVA melanoma. Shown are the lung weights on day 19 after challenge. (D) Representative images of the lungs of mice receiving different treatments. (E) LLN cells from C were analyzed for DC populations using FACS. The numbers of total CD8α+ DCs and CD11b+ DCs from mice (n = 4/group) are shown. Unless otherwise indicated, P values are shown as indicated.