A group of researchers identified two receptors that are critical for NK cell-mediated killing of melanoma cells. They found that melanoma cell lines express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1).
The NK cell subset of immune cells is known to contribute to the immune response that targets tumors. In the case of melanoma, however, it is yet to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination.
Scientists from The Babraham Institute, U.K., and the University of Catanzaro Magna Graecia, Italy, studied both human metastatic melanomas and spontaneous mouse melanomas. Their findings are detailed in the Journal of Clinical Investigation in a paper titled “NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo.”
They observed that human melanoma cell lines derived from lymph node metastases expressed proteins that interacted with the NK cell protein DNAM-1 and with a group of NK cell proteins known as NCRs. These cell lines were particularly susceptible to being killed by NK cells both in vitro and after being transplanted into mice.
Additionally, mouse spontaneous melanomas and melanoma cell lines both expressed proteins that bound DNAM-1 and NCRs. Further, interfering with the interaction of DNAM-1 and NCRs by antibody blockade or genetic disruption on melanoma cells reduced NK cell-mediated killing of human and mouse melanoma cells lines in vitro and in vivo.