Th9 cells promote antitumor immune responses in vivo

J Clin Invest. 2012 Nov;122(11):4160-71. doi: 10.1172/JCI65459. Epub 2012 Oct 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Immunity, Cellular*
  • Immunotherapy
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / pathology
  • Mice
  • Mice, Knockout
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology


  • CCL20 protein, mouse
  • CCR6 protein, mouse
  • Chemokine CCL20
  • Interleukin-9
  • Receptors, CCR6