The Participation of Transforming Growth Factor Beta in Tumor Immunoevasion

Abstract

In addition to exploring the clinical utility of combination cytokine therapies for the treatment of cancer, our studies also investigate the molecular mechanisms which participate in the generation of peripheral CD8+CD25 + T regulatory cells. Our findings suggest that in the presence of high concentrations of TGFbeta1, strong costimulatory strength is permissive for the induction of CD8+ T cells possessing suppressor functions. Our studies also demonstrate that the adoptive transfer of peripherally-induced regulatory CD8+ T cells into recipient mice may allow for the acceleration of pulmonary metastatic disease, suggesting that CD8+ T regulatory cells are capable of antagonizing antitumor immune responses in mice bearing metastatic melanoma. The findings from these collective studies advance our understanding of how antitumor immune responses may be enhanced through cytokine manipulation strategies, and characterize the molecular signals involved in peripheral CD8+ regulatory T cell development.