One subset of immune cells known to contribute to the immune response that targets tumors is the NK cell subset. Although this suggests that NK cell–based therapeutics have anticancer potential, more information is needed about the interactions between NK cells and human tumor cells if this promise is to be realized.
A team of researchers, at The Babraham Institute, United Kingdom, and the University of Catanzaro "Magna Graecia", Italy, has now provided insight into this issue by studying both human metastatic melanomas (aggressive forms of skin cancer that have spread to other sites) and spontaneous mouse melanomas.
The team, led by Francesco Colucci and Ennio Carbone, found 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.
Consistent with these data from human cell lines, 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 with proteins on melanoma cells reduced NK cell–mediated killing of human and mouse melanoma cells lines in vitro and in vivo. The authors therefore conclude that DNAM-1 and NCRs are critical for NK cell–mediated killing of melanoma cells and suggest that NK cells could be harnessed to prevent melanoma metastasis.
- NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. Journal Of Clinical Investigation, (in press)
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