Th9 cells promote antitumor immune responses in vivo
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
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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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 5

Th9 cells promote tumor-specific CD8+ CTL response in tumor-bearing mice.

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Th9 cells promote tumor-specific CD8+ CTL response in tumor-bearing mice...
(A–C) FACS analysis of the frequencies of CD8+ T cells staining positive for tumor infiltrating OVA tetramer (Kb-SIINFEKL), relative to total CD8+ T cells, (A) in therapeutic lung models, (B) in the total leukocytes in prophylactic s.c. tumor models when T cells were s.c. injected, or (C) in the total leukocytes in prophylactic s.c. tumor models when T cells were i.v. transferred. Graphs show the total number of tumor-infiltrating OVA tetramer–positive CD8+ T cells and/or granzyme B–producing CD8+ T cells in the leukocyte fraction. n = 4 mice/group. (D) PBS or 3 × 106 Th1 or Th9 cells were i.v. transferred into mice bearing 5-day established pulmonary B16-OVA melanoma. A group of mice transferred with Th9 cells also received depleting mAbs against CD8 every 3 days starting from 1 day before T cell transfer. Shown are the lung foci numbers observed on day 19 after challenge (n = 4 mice/group). Representative results from 1 of 2 performed experiments are shown. In D, P values indicate comparisons with PBS.