UCLA

Our previous research has shown that natural killer (NK) cells play a vital role as immune effectors in the selection and differentiation of various cancer stem cells and undifferentiated tumors. They achieve this through the direct killing and the release of IFN-γ and TNF-α, which inhibit tumor growth and curtail metastasis. Mechanistically, our studies have revealed that NK cells expanded by Osteoclasts display the ability to lyse CD4+ T cells while sparing CD8+ T cells, suggesting a potential selective effect of OC-activated NK cells on CD8+ T cell expansion. Consistent with these findings, we observed increased IFN-γ secretion, NK cell-mediated cytotoxicity, and higher proportions of CD8+ T cells in various tissue compartments of oral tumor-bearing hu-BLT mice following immunotherapy with OC-expanded NK cells. In this study, we focused on investigating the lytic and differentiation capabilities of supercharged NK (sNK) cells in ovarian cancer cell lines (OVCAR 4 and OVCAR 8), oral cancer cell lines (OSCC and OSCSC), and a pancreatic cancer cell line (MP 2). Our results demonstrated that sNK cells exhibited greater lysing activity against both poorly differentiated and well differentiated tumors compared to pNK cells treated with IL-2. Furthermore, the supernatants of sNK cells exhibited significantly higher levels of IFN-γ and induced differentiation by an increase in MHC class1 expressions in all the cell lines tested, except for OVCAR 8. Lastly, we observed a downmodulation of NKG2A and CD94 inhibitory receptors on sNK cells, suggesting potential alterations in their functional properties.