Myeloid derived suppressor cells as mediator of PAF‐R dependent systemic immunosuppression and melanoma tumor growth

Abstract

Previously, we have shown that ultraviolet B (UVB) irradiation induces systemic immunosuppression and augments the growth of experimental melanoma tumors via Tregs in a PAF‐R dependent manner. Myeloid derived suppressor cells (MDSC) are heterogeneous group of immature myeloid cells that are known to suppress host anti‐tumor immunity. However, its role in PAF‐R dependent systemic immunosuppression and melanoma tumor growth have not been investigated. The current studies were designed to determine if MDSC that are characterized by CD11b+Gr1+ cell markers (in mouse), mediate PAF‐R‐mediated effects. Using our well characterized models of contact hypersensitivity, we demonstrate that depletion of MDSC by anti‐Gr‐1 Ab abrogates PAF‐R agonists mediated systemic immunosuppression. As UVB or systemic PAF‐R agonists enhance CD11b+Gr‐1+ cell population in lymphoid organs, next studies investigated the role of MDSCs in PAF‐R‐dependent melanoma tumor growth. We observed that depleting Gr‐1+ cells, blocked both UVB and CPAF‐induced enhanced growth of melanoma tumors in WT mice. Interestingly, PAF‐R deficient mice showed substantial reduction in melanoma tumor growth by anti‐Gr‐1 Ab. These findings indicate that MDSC play crucial roles in PAF‐R agonists mediated systemic immunosuppression and melanoma tumor growth. Nevertheless, the crosstalks between MDSC and Tregs in PAF‐R dependent effects are under investigation, these studies provide novel insights into the mechanisms of PAF‐R induced effects.