The Importance of Chemokines Activating CXCR1, CXCR2 and CXCR3 in Tumorigenesis as Potential Therapeutic Targets in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.

Multiple myeloma (MM) is a neoplasm of plasma cells. Despite the development of increasingly advanced treatments, multiple myeloma remains challenging to cure completely. Consequently, the underlying mechanisms of this neoplasm are being investigated to identify new therapeutic targets and understand chemoresistance. A particular focus has been placed on the MM bone marrow microenvironment, with chemokines being one of its key components. This review examines the role of chemokines that activate the CXCR2 and CXCR3 receptors in both monoclonal gammopathy of undetermined significance (MGUS) and MM, highlighting all CXC chemokines and their receptors, including CXCL1, CXCL8/IL-8, CXCL9, CXCL10, and platelet factor 4. We focus on the direct effects of selected CXC chemokines on MM cells, specifically their roles in proliferation, migration, interaction with bone marrow cells, the formation of extramedullary disease, and chemoresistance. Additionally, we explore the impact of these chemokines on the MM bone marrow microenvironment, particularly in relation to mesenchymal stromal cells, myeloid-derived suppressor cells, osteoclasts, M2 macrophages, and natural killer cells, as well as processes such as bone destruction and angiogenesis. Finally, we discuss the potential use of drugs targeting the two chemokine axes described, with a focus on inhibitors and adoptive cell therapy.