NFAT1 supports tumor-induced anergy of CD4+ T cells

Brian T. Abe, Daniel S. Shin, Enric Mocholi, Fernando Macian

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Cancer cells express antigens that elicit T cell-mediated responses, but these responses are limited during malignant progression by the development of immunosuppressive mechanisms in the tumor microenvironment that drive immune escape. T-cell hyporesponsiveness can be caused by clonal anergy or adaptive tolerance, but the pathophysiological roles of these processes in specific tumor contexts has yet to be understood. In CD4+ T cells, clonal anergy occurs when the T-cell receptor is activated in the absence of a costimulatory signal. Here we report that the key T-cell transcription factor NFAT mediates expression of anergy-associated genes in the context of cancer. Specifically, in a murine model of melanoma, we found that cancer cells induced anergy in antigen-specific CD4+ T-cell populations, resulting in defective production of several key effector cytokines. NFAT1 deficiency blunted the induction of anergy in tumor antigen-speci fic CD4+ T cells, enhancing antitumor responses. These investigations identi fied tumor-induced T-cell hyporesponsiveness as a form of clonal anergy, and they supported an important role for CD4+ T-cell anergy in driving immune escape. By illustrating the dependence of tumor-induced CD4+ T-cell anergy on NFAT1, our findings open the possibility of targeting this transcription factor to improve the efficacy of cancer immunotherapy or immunochemotherapy.

Original languageEnglish (US)
Pages (from-to)4642-4651
Number of pages10
JournalCancer Research
Volume72
Issue number18
DOIs
StatePublished - Sep 15 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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