1α, 25 Dihydroxyvitamin D (1,25(OH)2D) Inhibits the T cell Suppressive Function of Myeloid Derived Suppressor Cells (MDSC)

Publication date: Available online 26 November 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): J.C. Fleet, G.N. Burcham, R.D. Calvert, B.D. Elzey, T.L. RatliffAbstractMyeloid derived suppressor cells (MDSC) suppress the ability of cytotoxic T cells to attack and clear tumor cells from the body. The active form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D), regulates myeloid cell biology and previous research showed that in mouse models 1,25(OH)2D reduced the tumor level of CD34+ cells, an MDSC precursor, and reduced metastasis. We tested whether MDSC are vitamin D target cells by examining granulocytic- (G-MDSC) and monocytic (M-MDSC) MDSC from tumors (TU), spleen (SP), and bone marrow (BM). Vitamin D receptor (VDR) mRNA levels are low in MDSC from bone marrow and SP but are 20-fold higher in TU MDSC. At all sites, M-MDSC have 4-fold higher VDR mRNA expression than G-MDSC. Bone marrow MDSC were induced to differentiate in vitro into tumor MDSC-like cells by treating with IFN-γ, IL-13, and GM-CSF for 48 h. This treatment significantly elevated Arg1 and Nos2 levels, activated the T cell-suppressive function of MDSC, increased VDR expression 50-fold, and made the MDSC responsive to 1,25(OH)2D treatment. Importantly, 1,25(OH)2D treatment reduced the T cell suppressive capacity of cytokine-induced total MDSC and M-MDSC by ≥70% and tumor-derived M-MDSC by 30-50%. Consistent with this finding, VDR deletion (KO) increased T cell suppressive f...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research