Nehla Banu
Mexico
Biography:
Abstract:
B7 homologue 6 (B7-H6) is a ligand for the NK cell activating receptor NKp30. Current research suggests that this ligand is selectively expressed on several cancer types including melanoma, prostate and cervical cancer, thus making it an important molecule to be studied further. It is known that B7H6 binding to NKp30 results in NK cell mediated cytotoxic killing of B7H6–expressing tumor cells. However, it is also interesting to note that the intracytoplasmic domain of B7H6 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) along with Src homology 2 (SH2) and src homology 3 (SH3) motifs, suggesting that this ligand may be involved in intracellular inhibitory signalling pathways. To investigate this idea, we stimulated B7H6 positive tumor cell lines with recombinant soluble NKp30 receptor, and evaluated possible inhibitory effects using the impedance RTCA system for cell proliferation, the scratch method for cell migration, and cytometry for apoptosis. As this B7H6 ligand is novel, we also tested the sensitivity of this ligand by detachment of the cells using EDTA, Accutase and triple express. Notably, we observed that use of EDTA and triplex for cell detachment gives the higher expression as compared to cell detachment with accutase. Also, we found that the sNKp30:B7H6 interaction significantly decreased tumor cell proliferation, migration rate and has no effect on apoptosis. We also showed an elevated level of soluble B7H6 in the cell supernatant, which may be a strategy of escaping NK cell mediated recognition and activation. In conclusion, we find that the ligand B7H6 may have a previously unknown inhibitory effect on tumor cells and may prove as an interesting target for cancer therapy.