Natural Killer cells: Future of Cancer Immunotherapy
Dr. Kawaljit Kaur
Division of Oral Biology and Medicine, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA.
Natural killer (NK) cells are known to target cancer stem cells and undifferentiated tumors. In this review, we discussed a novel strategy for expanding large numbers of super-charged NK cells with significant potential to lyse and differentiate cancer stem cells, and demonstrate the differences in the dynamics of NK cell expansion between healthy and cancer patients. Expansion and functional activation of super-charged NK cells by osteoclasts is dependent on NK receptors, their ligands on other immune cells, and secreted cytokines such as IL-12 and IL-15. NK cells from cancer patients have decreased surface receptor expression, especially NKG2D and CD16, and osteoclasts from cancer patients have reduced expression of NK receptor ligands ULBPs and MICA/B. Thus, in this report we not only provide a novel strategy to expand super-charged NK cells, but also demonstrate that rapid and sustained expansion of residual CD8+T cells within the purified NK cells during expansion with osteoclasts could be a potential mechanism by which the numbers and function of NK cells decline in cancer patients and in BLT humanized mice. Thus, restoration of NK cell numbers and function in cancer patients will be important to establish effective tumor control.