Comparison of Functional and Proliferative Activity of hTERT-NK and iCasp9-NK Cells

Abstract

Cancer progression is often accompanied with the acquisition of functional anergy by natural killer (NK) cells and their aging. As a result, persistent herpesviruses, such as hCMV and EBV, reactivate. The catalytic subunit of telomerase encoded by hTERT gene may enhance functional and proliferative activity. We aimed to elucidate if NK cells modified for sustained hTERT expression acquire these beneficial characteristics. We examined the proliferative and functional activities of hTERT-NK cells and combined observations with RNA-seq results. Thus, hTERT-NK cells were characterized with an increase in the expression levels of cell cycle genes and better proliferative activity in the third month after isolation. Increased degranulation upon K562 target cell recognition simultaneously with a higher expression level of granzyme B was observed for hTERT-NK cells. An increased level of IFNγ was also noted in hTERT-NK cells. These results reveal that hTERT-NK cells obtain additional advantages due to the stable hTERT expression. hTERT-NK cells are likely to perform high levels of functional activity over long time periods that are commonly needed during cancer treatment to perform immune surveillance and minimize relapse rates.