Role of natural killer cells in cancer and autoimmune diseases: Colorectal cancer and rheumatoid arthritis as a model

Natural killer (NK) cells have been described to play a critical role in cancer and autoimmune diseases. However, these cells face multiple obstacles in performing their cytolytic functions, such as inability to migrate towards cancer sites. Besides, the role of NK cells in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) has not been clearly identified. Hence, this study aimed at increasing NK cell migration to colorectal cancer sites and investigating NK cell markers that may aid in RA diagnosis. Recombinant chemokines and supernatants collected from the cell line HCT-116 were used in chemotaxis and calcium mobilization of NK92 cell line. Upon pretreatment of NK92 with dimethyl fumarate (DMF) or monomethyl fumarate (MMF), flow cytometry, western blot, qPCR and cytotoxicity assays were performed. In order to assess the role of NK cells in RA, in silico tools were used to identify genes that differentiate between various immune cells and NK cells, as well as NK cells of RA patients and healthy controls. This was validated on freshly isolated peripheral blood mononuclear cells and NK cells of healthy and RA individuals. CCL27, CCL28, CXCL16, and HCT-116 supernatants induced chemotaxis and mobilization of intracellular calcium in NK92 cells. Additionally, MMF or DMF pretreatment of NK92 cells upregulated the receptors CCR10 and CXCR6 and increased NK cytolytic activity. Besides, the identified genes were validated to be differentially expressed in NK cells compared to PBMCs as well as between NK cells of RA patients and healthy controls. In conclusion, this study aids in further understanding the potential role of NK cells in cancer and autoimmune diseases. Hence, our results suggest that NK cells could be harnessed as a tool for cancer immunotherapy and RA diagnosis.