| First Author | Abe BT | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 18 | Pages | 4642-51 |
| PubMed ID | 22865456 | Mgi Jnum | J:191294 |
| Mgi Id | MGI:5461417 | Doi | 10.1158/0008-5472.CAN-11-3775 |
| Citation | Abe BT, et al. (2012) NFAT1 supports tumor-induced anergy of CD4(+) T cells. Cancer Res 72(18):4642-51 |
| abstractText | 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-specific CD4+ T cells, enhancing antitumor responses. These investigations identified 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. |
