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 3

Therapeutic effect of tumor-specific Th9 cells.

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Therapeutic effect of tumor-specific Th9 cells. PBS or 3 × 106 Th1 or Th...
PBS or 3 × 106 Th1 or Th9 cells were transferred i.v. to C57BL/6 mice bearing 5-day established pulmonary B16-OVA melanoma. Mice (n = 4–5/group) were analyzed on day 19 after challenge. (A) Comparison of tumor foci numbers in the lung between treated mice. P = 0.042, Th1 versus Th9. (B) Number of total leukocytes, CD8+ T cells, and CD4+ T cells in the lung leukocyte fraction analyzed by FACS. P = 0.0014, Th1 versus Th9 for CD8+ T cells. (C) Expression of CD44 on CD4+ and CD8+ T cells from the LLN and lung leukocyte fraction. For Th1 versus Th9, P = 0.011 (LLN CD4+ T cells), P = 0.022 (LLN CD8+ T cells), P = 0.020 (lung CD4+ T cells), and P = 0.0035 (lung CD8+ T cells). (D) Cell numbers of myeloid population subsets in the lung leukocyte fraction analyzed by FACS. P = 0.00031, Th1 versus Th9 for CD8α+ DCs. (E) RT-PCR analysis of mRNA expression of chemokines and their receptors in the lung tumor tissues. Data shown were normalized to β-actin gene. For Th1 versus Th9, P = 0.014 (Ccl20), P = 0.025 (Ccr6). Representative results from 1 of 3 repeated experiments are shown. P values in the graphs show comparisons with PBS.