A key role of GARP in the immune suppressive tumor microenvironment.

ABSTRACT: In melanoma patients, one of the main reasons for tumor immune escape and therapy failure is the immunosuppressive tumor microenvironment. Herein, suppressive immune cells and inhibitory factors secreted by the tumor itself play a central role.In the present study we show that the Treg activation marker GARP (glycoprotein A repetitions predominant), known to induce peripheral tolerance in a TGF-β dependent way, is also expressed on human primary melanoma. Interestingly, membrane bound GARP is shed from the surface of both, activated Treg and melanoma cells, and, in its soluble form (sGARP), not only induces peripheral Treg but also a tumor associated (M2) macrophage phenotype. Notably, proliferation of cytotoxic T cells and their effector function is inhibited in the presence of sGARP. GAR

SUBMITTER: Hahn SA 

PROVIDER: S-EPMC5190003 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature