Rescue of notch-1 signaling in antigen-specific CD8+ T cells overcomes tumor-induced T-cell suppression and enhances immunotherapy in cancer.

ABSTRACT: An impaired antitumor immunity is found in patients with cancer and represents a major obstacle in the successful development of different forms of immunotherapy. Signaling through Notch receptors regulates the differentiation and function of many cell types, including immune cells. However, the effect of Notch in CD8(+) T-cell responses in tumors remains unclear. Thus, we aimed to determine the role of Notch signaling in CD8(+) T cells in the induction of tumor-induced suppression. Our results using conditional knockout mice show that Notch-1 and Notch-2 were critical for the proliferation and IFNγ production of activated CD8(+) T cells and were significantly decreased in tumor-infiltrating T cells. Conditional transgenic expression of Notch-1 intracellular domain (N1IC) in antigen-specif

SUBMITTER: Sierra RA 

PROVIDER: S-EPMC4125513 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature