Simulated microgravity impairs human NK cell cytotoxic activity against space radiation-relevant leukemic cells

Natural killer (NK) cells are an important first-line of defense against malignant cells. Because of the potential for increased cancer risk from astronaut exposure to space radiation, we determined whether microgravity present during spaceflight affects the body's defenses against leukemogenesis. Human NK cells were cultured for 48 h under normal gravity and simulated microgravity (sμG), and cytotoxicity against K-562 (CML) and MOLT-4 (T-ALL) cells was measured using standard methodology or under continuous sμG. This brief exposure to sμG markedly reduced NK cytotoxicity against both leukemias, and these deleterious effects were more pronounced in continuous sμG. RNA-seq performed on NK cells from two additional healthy donors provided insight into the mechanism(s) by which sμG reduced cytotoxicity. Given our prior report of space radiation-induced human T-ALL in vivo, the reduced cytotoxicity against MOLT-4 is striking and raises the possibility that μG may increase astronaut risk of leukemogenesis during prolonged missions beyond LEO.