Suppressing MDSC Recruitment to the Tumor Microenvironment by Antagonizing CXCR2 to Enhance the Efficacy of Immunotherapy

SIMPLE SUMMARY: While the development of immunotherapy has greatly advanced cancer treatment, many patients do not benefit from immunotherapy. Numerous strategies have been developed to improve response to immunotherapy across cancer types, including blocking the activity of immunosuppressive immune cells, cytokines, and signaling pathways that are linked to poor responses. Myeloid-derived suppressor cells (MDSCs) are associated with poor responses to immunotherapy, and the chemokine receptor, CXCR2, is involved in recruiting MDSCs to the tumor. In this review, we present studies that explore the potential of inhibiting MDSCs through blocking CXCR2 as a strategy to enhance response to existing and novel immunotherapies. ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells derived from immature myeloid cells. These cells are often associated with poor responses to cancer therapy, including immunotherapy, in a variety of tumor types. The C-X-C chemokine receptor 2 (CXCR2) signaling axis plays a key role in the migration of immunosuppressive MDSCs into the tumor microenvironment (TME) and the pre-metastatic niche. MDSCs impede the efficacy of immunotherapy through a variety of mechanisms. Efforts to target MDSCs by blocking CXCR2 is an active area of research as a method for improving existing and novel immunotherapy strategies. As immunotherapies gain approval for a wider array of clinical indications, it will become even more important to understand the efficacy of CXCR2 inhibition in combating immunotherapy resistance at different stages of tumor progression.