Depletion of Polymorphonuclear Myeloid-Derived Suppressor Cells Increases Efficacy of Listeria monocytogenes Cancer Vaccine

Abstract The tumor microenvironment is highly immunosuppressive, allowing cancer to evade the immune system by inducing dysfunction, exhaustion, or subversion of CD8+ T-cell functions. Cancer immunotherapies using attenuated strains Listeria monocytogenes (Listeria) engineered express antigens have been demonstrated promote antigen-specific T-cells that infiltrate and control mouse models cancer. However, in human clinical trials, initial IV therapies utilizing did not demonstrate strong efficacy, suggesting generation tumor-specific recognizing alone insufficient provide robust control. Here, we intratumoral (IT) intravenous (IV) inoculation an form Listeria(ΔActA) no therapeutic benefit context establish MC38 tumor-bearing mice while predominantly recruiting infecting CD11b+Ly6G+CD14+ cells microenvironment, markers associated with polymorphonuclear myeloid-derived suppressor (PMN-MDSCs). In vitro analysis PMN-MDSC infection revealed increased immunosuppressive function, indicating a possible adverse outcome treatment vivo. Further, IT injection depletion efficacy therapy promoted mediated anti-tumor response. Collectively, our results PMN-MDSCs may be required mediate immunotherapy production effective Supported grants from NIH (DP2CA247830) & Research Coordinating Committee (CRCC) (C23CR5612)