Tumor-Released Survivin Induces a Type-2Â T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro

Clinical studies of T cell profiles from cancer patients have shown a skewing toward a type-2Â T cell response with decreased cytotoxic T cell function. However, the primary cause of this shift remains unknown. Here we show that tumor-released Survivin, an inhibitor of apoptosis (IAP) protein and tumor-specific antigen, is taken up by T cells and alters their response. The addition of Survivin to T cell cultures resulted in decreased T cell proliferation and reduced cytotoxic CD8^sup +^ T cell function. Additionally, type 1 cell numbers and IFN-[gamma] and IL-2 production were significantly reduced, while IL-4 release and type 2Â T cell numbers increased. In contrast, the function and numbers of Th17 and T regulatory cells were not affected. These studies show that tumor-released Survivin modulates T cells resulting in a phenotype similar to that observed in cancer patients with a polarity shift from a type 1 to a type 2 response.[PUBLICATION ABSTRACT]