Tumor-specific Th17-polarized cells eradicate large established melanoma

ABSTRACT: CD4+ T cells can differentiate into multiple effector subsets but the potential roles of these subsets in anti-tumor immunity have not been fully explored. We sought to study the impact of CD4+ T cell polarization on efficacy of tumor rejection in a model closely mimicking human disease where the target antigens are often non-mutated tissue differentiation self-antigens. We generated a new transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen that is expressed by normal melanocytes and B16 murine melanoma. We found that cells could be robustly polarized into Th0, Th1 and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles as well as by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells play the most important role in tumor rejection, we found that Th17-polarized cells were superior in mediating destruction of advanced B16 melanoma. Unexpectedly, their therapeutic effect was critically dependent on IFN-γ production, while depletion of IL-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for the successful tumor eradication. This principle should be taken under consideration in the design of future clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Two-condition experiment: RNA from TRP-1 transgenic mouse lymphocytes polarized to be either Th1 or Th17 were compared to cells polarized to be Th0. Keywords: Lymphocyte polarization comparison

ORGANISM(S): Mus musculus

PROVIDER: GSE10814 | GEO | 2008/03/15

SECONDARY ACCESSION(S): PRJNA107409

REPOSITORIES: GEO