Distinct NK Cell Function and Gene Expression in Children with Acute Lymphoblastic Leukemia in Remission Before and After Acute Exercise

Children and adolescents who have acute lymphoblastic leukemia (ALL), often display an impaired natural killer cell (NK) function. Brief bouts of exercise mobilize NK cells and influence their gene expression, but little is known about the effect of exercise on NK cell function and gene expression in pediatric ALL survivors, which remains unclear. This study examined the effect of exercise on NK gene expression and cytotoxic activity (NKCA) in pediatric ALL patients in remission. Nine B-cell ALL children in remission and 9 sex and age-matched healthy controls with no history of cancer (14.8±1 and 15±1 y/o, respectively; 2 girls per group) performed eight 2-min bouts of cycle ergometry at 60% of peak work rate (71±2% of V̇O 2 peak) interspersed with 1-min rest intervals. Circulating NK cells gene expression profile (RNA-seq) and NKCA (in vitro) were performed before and after exercise. NK cell function (NK cell cytotoxicity assay) and gene expression (RNAseq) analyses were performed. Exercise altered the expression of thousands of NK cell genes in both ALL and controls, with a distinct pattern in ALL both at baseline (294 Genes) and in response to exercise (179 genes). At baseline, nine gene pathways involved in NK cell function were affected, and following exercise, 28 pathways related to inflammatory response and cancer were impacted. NKCA was lower at baseline in survivors compared to controls. The reduced activity was partially mitigated following exercise but remained lower in ALL compared to controls. Exercise may improve NK cell function, specifically in immune surveillance in ALL children in remission, and has the potential to be used as adjunctive therapy in ALL. The differential gene expression response to exercise suggest that NK cells in ALL may adopt a different molecular strategy to fight infections or tumors.