Influence of SLAM Family Receptors in the NK-Cell-Mediated Surveillance of Lymphoblastic Acute Leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide. Along with other lymphocytes, NK cells have important functions in the recognition and elimination of malignant cells, and thus are of interest for the development of novel therapeutic treatments of various cancers, including leukemia. The signaling lymphocyte activation molecule (SLAM) family includes surface molecules that are expressed in hematopoietic cells, where they regulate distinct cell responses. Altered expression and/or function of these receptors may be involved in the etiology of several diseases. Here we report the altered overall expression of SLAM family receptors (SFR) in leukemia cells from pediatric patients. Additionally, we found that the expression of a single type of SLAM receptor in leukemia target cells was sufficient to upregulate the release of cytotoxic granules from primary NK cells. Moreover, coating the leukemia cell surface with specific engagers containing recombinant SFR was sufficient to enhance NK-cell degranulation and unleash the cytotoxic competence of primary NK cells from ALL patients. Finally, the NK effector responses promoted by SLAM receptor engagement were dependent on the ability to recruit PLC-γ. Overall, these findings suggest that SFR are a promising resource for the treatment of pediatric acute lymphoblastic leukemia.