Radiation-induced autophagy potentiates immunotherapy of cancer via up-regulation of mannose 6-phosphate receptor on tumor cells in mice.

ABSTRACT: There is a significant body of evidence demonstrating that radiation therapy (XRT) enhances the effect of immune therapy. However, the precise mechanisms by which XRT potentiates the immunotherapy of cancer remain elusive. Here, we report that XRT potentiates the effect of immune therapy via induction of autophagy and resultant trafficking of mannose-6-phopsphate receptor (MPR) to the cell surface. Irradiation of different tumor cells caused substantial up-regulation of MPR on the cell surface in vitro and in vivo. Down-regulation of MPR in tumor cells with shRNA completely abrogated the combined effect of XRT and immunotherapy (CTLA4 antibody) in B16F10-bearing mice without changes in the tumor-specific responses of T cells. Radiation-induced MPR up-regulation was the result of redistribu

SUBMITTER: Kim S 

PROVIDER: S-EPMC4330093 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature