CD4+ T-cell-mediated anti-tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis

Sheng Zhang, Dannie Bernard, Waliul I. Khan, Mark H. Kaplan, Jonathan L. Bramson, Yonghong Wan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Previous reports have suggested that autoimmune sequelae may be an unavoidable consequence of successful immunization against tumor-associated antigens, which are typically non-mutated self-antigens. Using a melanoma model, we demonstrated that CD4+ T-cell-mediated anti-tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis. Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti-tumor immunity is mediated via a STAT6 and IL-4-dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN-γ. Our results offer a possibility to elicit specific anti-tumor responses without triggering unwanted tissue autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1252-1259
Number of pages8
JournalEuropean Journal of Immunology
Volume39
Issue number5
DOIs
StatePublished - May 1 2009

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Keywords

  • Anti-tumor immunity
  • Autoimmunity
  • CD4 T cells
  • Cytokines
  • Vaccination

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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