Purpose: To evaluate the impact of Vemurafenib on myeloid derived suppressor cell (MDSC) populations in patients with advanced melanoma.

Experimental Design: Ex vivo MDSCs were obtained from PBMCs of late stage melanoma patients treated with Vemurafenib as well as healthy controls. The frequency and phenotype of MDSCs was determined by flow cytometry. MDSC populations were characterized for their suppressive function on autologous T cells in CFSE proliferation assays. Additionally, conditioned medium of a melanoma cell line treated with Vemurafenib or not was studied for its effect on MDSCs in vitro.

Results: In comparison to healthy donors, patient PBMCs showed an increased frequency of CD14+HLA-DR−/low monocytic MDSCs (moMDSCs) and of a previously unrecognized population of CD14CD66b+Arginase1+ granulocytic MDSCs (grMDSCs). In vitro, both populations suppressed autologous T-cell proliferation. Vemurafenib treatment of melanoma patients reduced the frequency of both moMDSCs and grMDSCs. Accordingly, conditioned medium from Vemurafenib treated melanoma cells was less active in inducing moMDSCs in vitro.

Conclusion: Patients with advanced melanoma show increased levels of moMDSCs, as well as a population of CD14CD66b+Arginase1+ grMDSCs. Both MDSCs are distinct populations capable of suppressing autologous T-cell responses independently of each other. In vitro as well as in vivo, Vemurafenib inhibits the generation of human moMDSCs. Thus, Vemurafenib decreases immunosuppression in patients with advanced melanoma, indicating its potential as a part of future immunotherapies.

Citation Format: Bastian Schilling, Antje Sucker, Klaus Griewank, Fang Zhao, Benjamin Weide, Andre Görgens, Bernd Giebel, Dirk Schadendorf, Annette Paschen. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4714. doi:10.1158/1538-7445.AM2013-4714