Abstract IA13: Immune suppressive and immune stimulating monocytes in cancer

Abstract

Abstract The tumor environment is enriched in myeloid cells, which can either promote or fight tumor progression. By releasing soluble mediators—such as cytokines, interleukins, metabolites, and growth factors—tumors stimulate a reactive myelopoiesis at both medullary and extra-medullary sites such as the spleen, which alters the steady-state myeloid differentiation, pushing proliferation and expansion of myeloid elements that acquire immunosuppressive and pro-tumoral functions. This process is regulated by the fine balance between pro-survival and anti-apoptotic programs in myeloid cells. The frequency and the function of myeloid-derived suppressor cells (MDSC) in the blood of tumor patients is now regarded as a negative prognostic marker, which correlates with the clinical outcome and response to therapy, including both conventional chemotherapy as well as immunotherapy. Recent data suggest that the monocytic compartment within MDSC (M-MDSC) in tumor-conditioned hosts is extremely plastic. Different pathways activated in M-MDSC, including the metabolism of the semi essential amino acid L-arginine, exert a negative influence on the proliferation and functions of antigen-stimulated T lymphocytes. In fact, the inability of T lymphocytes to recognize and destroy tumor cells can depend on the suppressive milieu shaped by the two enzymes involved in L-arginine metabolism. On the other hand, nitric oxide-producing cells derived from monocytes can support cancer cell destruction and tumor regression. In fact, even though tumor-specific CD8+ T cells are negatively influenced by intra-tumoral L-arginine metabolism, they can license a subset of monocytes to aid tumor rejection, which depends on increased tumor antigen presentation and nitric oxide synthase 2 induction, as the result of the intratumor activation of the CD40-CD40L axis. Understanding the molecular events and cell biology of immune stimulating and immune suppressive monocytes can provide additional targets to modify the tumor environment and enhance cancer immunotherapy. Citation Format: Vincenzo Bronte. Immune suppressive and immune stimulating monocytes in cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA13.