NK cell surveillance of hematological malignancies. Therapeutic implications and regulation by chemokine receptors

Abstract

NK cells are circulating innate lymphoid cells that constantly move from bloodstream into tissues, exerting several functions including tumor surveillance. For this reason, NK cells are considered attractive target for cancer immunotherapy. Several strategies are employed to harness NK cell efficacy especially in hematological tumors, including adoptive transfer, genetic manipulation to overexpress chimeric antigen receptors and cytokine or immunomodulatory drug treatments of ex-vivo cultivated and expanded NK cells. Several chemokine receptors support NK cell tissue homing and are required for efficient tumor infiltration. Nevertheless, chemokine receptor expression is often insufficient, or their respective ligands may not be expressed in the tumor microenvironment, thus limiting NK cell localization at the tumor site. Therefore, strategies to implement expression or promote the function of the correct chemokine receptor/ligand axes have been employed in the last years with promising results in preclinical models. In this review, we discuss how chemokine receptors and their ligands regulate the trafficking and localization of NK cells in hematological tumors and how the chemokine function can be manipulated to improve current therapeutic approaches.

Keywords: Bone marrow; CAR-NK; Chemokine receptors; Immunotherapy; Leukemia; Multiple myeloma; Natural killer cells; Tumor microenvironment.