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 4

Th9 cells maintain cytokine expression profile in tumor-bearing mice.

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Th9 cells maintain cytokine expression profile in tumor-bearing mice. (A...
(A) PBS or 3 × 106 Th1 or Th9 cells were i.v. transferred to mice (wild-type and Ifng–/– mice) with 5-day established pulmonary B16-OVA melanoma. On day 4 after transfer, total LLN and lung cells were harvested and restimulated with OVA peptides for 36 hours. Cytokine levels in culture supernatants were tested using ELISA. (B) OVA-specific CFSE-labeled Th1 or Th9 cells (3 × 106) were i.v. transferred into mice with 5-day pulmonary B16-OVA melanoma. On day 4 after transfer, CFSE+ Th1 or Th9 cells and CFSE– endogenous cells were sorted from LLNs with flow cytometer. CFSE+ Th1 or Th9 cells were maintained with 10 U/ml IL-2, and CFSE– cells were restimulated with 5 μg/ml OVA323–339 and OVA257–264 peptides for 36 hours. Cytokine levels in the supernatant were tested using ELISA. (C) mAbs neutralizing IL-9, IL-10, or control IgG were i.p. injected to C57BL/6 wild-type mice bearing 5-day established pulmonary B16-OVA melanoma; some groups of mice were also i.v. transferred with 3 × 106 Th9 cells. The graph shows the comparison of the numbers of tumor foci in the lungs of mice (n = 4/group) receiving the indicated treatments. Representative results from 1 of 2 performed experiments are shown.