Immunological consequences of selective BRAF inhibitors in malignant melanoma: Neutralization of myeloid-derived suppressor cells

Bastian Schilling, Annette Paschen, Bastian Schilling, Annette Paschen

Abstract

Myeloid-derived suppressor cells (MDSC) potently repress antitumor immunity. The amount of MDSC in the blood of melanoma patients declines in response to vemurafenib, an inhibitor of oncogenic BRAF signaling that abrogates the ability of malignant cells to induce MDSC. This suggests that vemurafenib may be used in combination with various immunotherapeutic agents for the induction of long-lasting tumor regression.

Keywords: BRAF; grMDSC; melanoma; moMDSC; myeloid-derived suppressor cells; vemurafenib.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3805652/bin/onci-2-e25218-g1.jpg
Figure 1. Vemurafenib abrogates the immunosuppressive effects of MDSC in melanoma patients. Vemurafenib inhibits mutant BRAFV600E signaling in melanoma cells, not only limiting their proliferation and survival, but also interfering with the secretion of soluble factors that are responsible for the recruitment, induction and differentiation of myeloid-derived suppressor cells (MDSC). Vemurafenib appears to have no direct effects on MDSC induction, though a potential modulation of MDSC function by vemurafenib has not been studied yet.

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Source: PubMed

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