Natural killer (NK) cells and anti-tumor therapeutic mAb: unexplored interactions

Tumor-targeting mAb are widely used in the treatment of a variety of solid and hematopoietic tumors and represent the first immunotherapeutic approach successfully arrived to the clinic. Nevertheless, the role of distinct immune mechanisms in contributing to their therapeutic efficacy is not completely understood and may vary depending on tumor- or antigen/antibody-dependent characteristics. Availability of next-generation, engineered, tumor-targeting mAb, optimized in their capability to recruit selected immune effectors, re-enforces the need for a deeper understanding of the mechanisms underlying anti-tumor mAb functionality. NK cells participate with a major role to innate anti-tumor responses, by exerting cytotoxic activity and producing a vast array of cytokines. As the CD16 (low-affinity FcγRIIIA)-activating receptor is expressed on the majority of NK cells, its effector functions can be ideally recruited against therapeutic mAb-opsonized tumor cells. The exact role of NK cells in determining therapeutic efficacy of tumor-targeting mAb is still unclear and much sought after. This knowledge will be instrumental to design innovative combination schemes with newly validated immunomodulatory agents. We will summarize what is known about the role of NK cells in therapeutic anti-tumor mAb therapy, with particular emphasis on RTX chimeric anti-CD20 mAb, the first one used in clinical practice for treating B cell malignancies.