ADP secreted by dying melanoma cells mediates chemotaxis and chemokine secretion of macrophages via the purinergic receptor P2Y12.

ABSTRACT: Melanoma immunotherapy is still not satisfactory due to immunosuppressive cell populations within the tumor stroma. Targeting tumor-associated macrophages (TAM) can help to restore an anti-tumor immunity. Previously, we could show that classical TAM markers expressed in vivo need a 7 day M-CSF/dexamethasone/IL-4 (MDI) stimulation for their induction in peripheral blood monocytes (pBM) in vitro. To identify possible novel therapeutic targets on TAM, gene expression analysis of MDI-treated pBM was performed. This identified up-regulation of the purinergic G-protein coupled receptor P2Y12, the therapeutic target of the clinically approved anti-thrombotic drugs cangrelor, clopidogrel, ticagrelor, and prasugrel. We generated a peptide antibody and validated its specificity using transgenic P2Y1

SUBMITTER: Kloss L 

PROVIDER: S-EPMC6779894 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature