J. F. Calata1, S. Jayaraman1, B. S. Prabhakar1, A. V. Maker1 1University Of Illinois At Chicago,Chicago, IL, USA
Introduction:
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that negatively regulate immune responses during tumor progression. There remains a significant gap in our understanding of their phenotypical and functional heterogeneity. We have previously demonstrated that the immunostimulatory cytokine LIGHT (TNFSF14) can mature certain myeloid cells, and that its presence in the tumor microenvironment can stimulate an anti-tumor T-cell response. We, therefore, determined to define the expression of LIGHT and its cognate receptors on MDSCs.
Methods:
Female BALB/c mice, 6-8 weeks of age, were injected subcutaneously with 1×106 CT26 cells (murine colorectal carcinoma cell line). When tumors reached 1 cubic centimeter, splenectomy was performed. Splenocytes were isolated and evaluated with flow cytometry for expression CD11b, Ly6G, Ly6C, HVEM, LTBR, and LIGHT.
Results:
Monocytic-MDSC (M-MDSC, CD11b+/Ly6G+) and granulocytic-MDSCs (G-MDSC, CD11b+/Ly6C+) were identified in tumor bearing mice. LIGHT was expressed preferentially on G-MDSCs (94% vs. 39%, p= 0.0006). The LIGHT receptors HVEM and LTBR were also expressed on MDSC subsets. LTBR expression was high in both populations, but increased in G-MDSC compared to M-MDSC (p=0.018), while HVEM expression was lower in G-MDSC (84% vs. 40%, p=<0.0001). Populations of M-MDSC were, therefore, characterized as LIGHTlowLTBRlowHVEMhi while G-MDSC were LIGHThiLTBRhiHVEMlow.
Conclusion:
MDSCs can be characterized by their expression of LIGHT and its cognate receptors. Based on this data, the effect of LIGHT and LIGHT receptor blockade on MDSC function warrants further investigation since inhibition of immunosuppressive MDSC may be a promising strategy for tumor immunotherapy.
