Immune-mediated eradication of tumors through the blockade of transforming growth factor-β signaling in T cells

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Abstract
Despite the existence of tumor-specific antigens and demonstrated presence of tumor-specific immune cells, the majority of tumors manage to avoid immune-mediated destruction. Various mechanisms have been suggested for tumor evasion from immune response. One such mechanism is thought to be mediated by transforming growth factor-β (TGF-β), an immunosuppressive cytokine found at the site of most tumors. We demonstrate here that T-cell–specific blockade of TGF-β signaling allows the generation of an immune response capable of eradicating tumors in mice challenged with live tumor cells. In addition, we provide mechanisms through which abrogation of TGF-β signaling leads to the enhancement of anti-tumor immunity. Our data indicate that T-cell–specific blockade of TGF-β signaling has strong therapeutic potential to shift the balance of the immune response in favor of anti-tumor immunity.