Methods: Using 51Cr release assay, PCR, multiplex cytokine arrays and flowcytometry we established the potential contribution of Fc receptor triggering on NK cells in growth and resistance of oral tumors.
Results: Naïve NK cells lose their cytotoxic function and undergo rapid apoptosis upon treatment with intact as well as F (ab)'2 fragment of anti-CD16 antibodies. Addition of IL-2 in combination with anti-CD16 antibodies significantly inhibited anti-CD16 antibody mediated DNA fragmentation, and partially prevented the decrease in NK cell function. There was a significant increase in Fas Ligand, TNF-α and IL-6 but not those of Granzymes A and B, Perforin and Trail genes in NK cells treated with anti-CD16 antibodies. Neither induction of CD69 activation antigen nor increased secretion of IFN-γ could be observed after the treatment of NK cells with anti-CD16 antibodies. Finally, addition of anti-CD16 antibodies upon co-cultures of NK cells with tumor target contributed potently to the induction of VEGF and TNF-α secretion by oral tumor cells.
Conclusion: The results indicate that NK cells which are triggered to undergo cell death by oral tumors are capable of supporting the growth and development of the tumors. Therefore, this would be one mechanism by which chronic inflammation could contribute to tumorigenesis.