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 2

Prophylactic effect of tumor-specific Th9 cells.

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Prophylactic effect of tumor-specific Th9 cells. (A) OVA-specific Th9 ce...
(A) OVA-specific Th9 cells used in each experiment typically contained about 25% IL-9–expressing CD4+ OT-II T cells. (B–F) C57BL/6 mice (n = 4–5/group) received PBS or 3 × 106 Τh9 cells on the same day when mice were i.v. challenged with 1 × 105 B16-OVA cells, and were analyzed on day 19 after challenge. (B) Comparison of tumor foci numbers in the lung between PBS- and Th9 cell–treated mice. (C) Number of total leukocytes, CD8+ T cells, and CD4+ T cells in the lung leukocyte fraction analyzed by FACS. (D) Cell numbers of myeloid population subsets in the lung leukocyte fraction analyzed by FACS. (E) Expression of CD44 on CD4+ and CD8+ T cells from the lung. (F) RT-PCR analysis of mRNA expression of chemokines and their receptors in lung tumor tissues. Data shown were normalized to the β-actin gene. (G) Th1 or Th9 cells (2 × 106) were s.c. injected on the same day and at the same location where 5 × 105 B16-OVA tumor cells had been implanted s.c. Tumor growth curves are shown. P = 0.0033 for Th1 versus Th9 on day 21. (H) Th1 or Th9 cells (3 × 106) were i.v. transferred on the same day that 2 × 105 B16-OVA tumor cells were s.c. injected. Tumor growth curves are shown. P = 0.012 for Th1 versus Th9 on day 21. Representative results from 1 of 3 repeated experiments are shown. The P values in the graphs show comparisons with PBS.