Tumor-released survivin induces a type-2 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-2 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(+) T cell function. Additionally, type 1 cell numbers and IFN-γ and IL-2 production were significantly reduced, while IL-4 release and type 2 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.
Center for Health Disparities & Molecular Medicine, Department of Basic Sciences, Loma Linda University, 11085 Campus Street, Mortensen Hall Room 162, Loma Linda, CA, 92350, USA.
Jessica M S
JM
Jutzy
Salma
S
Khan
Malyn May
MM
Asuncion-Valenzuela
Terry-Ann M
TA
Milford
Kimberly J
KJ
Payne
Nathan R
NR
Wall