Cytokine treatment of macrophage suppression of the Mls response (88.3)

Components of the immune system essential for curbing tumor progression are often found within the tumor. High macrophage to T cell ratios (Mö:T) are hallmarks of the tumor microenvironment. We have shown that such conditions suppress the immune response to the retroviral superantigen Mls by IFN ã -triggered production of the Arg- and Trp-consuming enzymes iNOS and IDO. In attempts to reverse suppression by treatment with pro-inflammatory cytokines, IL-6 improved the T cell response to Mls, IL-1 and TNFá had little effect, and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mö expression of CD80, a significant ligand for the immunosuppressive B7H1 and CTLA-4 receptors. These results reveal avenues for reversal of the suppression of cell-mediated immunity characteristic of the high Mö:T cell ratios found in many tumors. Supported by NIH AREA R15-AI060356-01.