A key role of GARP in the immune suppressive tumor microenvironment
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Author
Hahn, Susanne A.
Neuhoff, Annemarie
Landsberg, Jenny
Schupp, Jonathan
Eberts, Daniela
Leukel, Petra
Bros, Matthias
Weilbaecher, Martin
Schuppan, Detlef
Grabbe, Stephan
Tueting, Thomas
Lennerz, Volker
Sommer, Clemens
Jonuleit, Helmut
Tuettenberg, Andrea
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.18632/oncotarget.9598Metadata
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Hahn, S. A., A. Neuhoff, J. Landsberg, J. Schupp, D. Eberts, P. Leukel, M. Bros, et al. 2016. “A key role of GARP in the immune suppressive tumor microenvironment.” Oncotarget 7 (28): 42996-43009. doi:10.18632/oncotarget.9598. http://dx.doi.org/10.18632/oncotarget.9598.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. GARP expression on Treg and melanoma cells is significantly decreased in the presence of agents such as IFN-α, thus explaining at least in part a novel mechanism of action of this adjuvant therapy. In conclusion, GARP in its soluble and membrane bound form contributes to peripheral tolerance in a multipronged way, potentiates the immunosuppressive tumor microenvironment and thus acts as a negative regulator in melanoma patients. Therefore, it may qualify as a promising target and a new checkpoint for cancer immunotherapy.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190003/pdf/Terms of Use
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