Scavenger receptor A is involved in tumor associated immune suppression (TUM6P.958)

Abstract

Abstract Tumors activate a plethora of immunosuppressive mechanisms to counteract effective immune responses, e.g. establishing T cell tolerance against tumor antigens or inducing the expansion of T-cell suppressive cell populations, in particular myeloid derived suppressor cells (MDSCs). Our previous studies have demonstrated that scavenger receptor A (SRA) dampened the intrinsic immunogenicity of antigen presenting cells. To determine the potential involvement of SRA in tumor-mediated immune suppression, we examine the expression of SRA on MDSCs during tumor progression and its impact on the suppressive activity of MDSCs. We show that expansion of MDSCs in tumors and peripheral lymphoid organs (e.g., spleen) is dependent on tumor size. SRA is predominantly expressed on monocytic MDSCs (not granulocytic population), which shows a positive correlation with tumor development. Regardless of tumor growth stages, SRA expression in tumor infiltrating MDSCs is substantially higher compared with their counterparts in lymphoid tissues. Interestingly, tumor growth-dependent elevation of SRA expression correlates with the T-cell suppressive activity of MDSCs. Additionally, the absence of SRA strongly promotes the therapeutic efficacy of adoptively transferred tumor-reactive T cells. Our findings suggest that SRA may participate in tumor-mediated immunosuppressive mechanisms and contribute to the immune evasion during cancer progression.