The Effect Of Acute Exercise And Hypoxia On Natural Killer Cell Cytotoxic Function Against Tumors Expressing Different Levels Of Major Histocompatibility Complex (mhc) Molecules

Solid tumors promote hypoxia in their microenvironment, which is closely associated with metastatic progression and immune system evasion. Tumors can also evade Natural Killer (NK) cells by altering their expression of Major Histocompatibility Complex (MHC) molecules. Although acute exercise has been shown to improve NK cell function against HLA-deficient cell lines under normoxic conditions, whether exercise increases NK cell cytotoxicity against tumors expressing high levels of MHC molecules, such as Triple Negative Breast Cancer (TNBC) cell line MDA-MB-231 under hypoxia is unknown. PURPOSE: To examine the effects of an acute bout of exercise on NK cell specific lysis under normoxic or hypoxic conditions against 1) HLA-deficient leukemia K562 cells, 2) a low MHC-expressing MCF-7 cells, and 3) High MHC-expressing MDA-MB-231 cells. METHODS: Thirteen inactive healthy women (mean ± SD: n = 13, age 26.9 ± 4.5 y) cycled at 10% above their lactate threshold for 30 min. Resting and post-exercise NK cells were isolated and co-cultured for 4 hours with K562, MCF-7, and MDA-MB-231 cells in either hypoxic (H: 1% of O2) or normoxic conditions (N: 21% of O2). RESULTS: Acute exercise increased NK cell killing of K562 cells under normoxic and hypoxic conditions (p < 0.01, p < 0.05, resp); however, post-exercise NK cells killed fewer K562 cells when cultured under hypoxic conditions than normoxic conditions (17.88 ± 8.46% vs. 24.28 ± 11.62%; p < 0.01). Both normoxic- and hypoxic-cultured post-exercise NK cells showed an increased killing against MCF-7 cells compared to resting NK cells (p < 0.05, p < 0.01, respectively). However, post-exercise NK cells killing of MCF-7 was not different in hypoxia than those in normoxia (18.55 ± 10.83% vs. 22.68 ± 9.47%, p = 0.214). When cultured under normoxic conditions, acute exercise did not affect NK cells’ killing of MDA-MB-231 cells. However, specific lysis of post-exercise NK cells under hypoxia was increased in response to exercise (10.67 ± 7.63% vs. 7.80 ± 5.27%; p < 0.05). CONCLUSION: Our data suggest that a single bout of exercise increases NK cell killing of high MHC-expressing TNBC cell lines in hypoxic conditions and partially rescues the hypoxic-derived alterations of NK cell killing ability against cell line with no (K562) or low MHC expression (MCF-7) of MHC.