Role of myeloid-derived suppressor cells in tumor immunotherapy

Abstract

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that infiltrate human and experimental tumors and strongly inhibit anticancer immune response directly or by inducing regulatory T-lymphocyte activity. Consequently, MDSCs are important actors of cancer-induced immune tolerance and a major obstacle to efficiency of cancer immunotherapy. Several means of preventing MDSCs accumulation or inhibiting their immunosuppressive effect were recently discovered in cancer-bearing hosts, contributing to restoring antitumor immunity and consequently to control of tumor growth. In experimental tumor models, targeting MDSCs can enhance the effects of active or passive immunotherapy. While similar effects have not yet been noted in cancer-bearing patients, recent preclinical findings demonstrating that the selective toxicity of conventional chemotherapies such as gemcitabine and 5-fluorouracil on MDSCs might contribute to their anticancer effect provide impetus to pursue investigations to unravel novel therapeutics that target MDSCs in humans.