Natural Killer Cell Function In Mice With Pancreatic Cancer Does Not Differ With Exercise Training

Moderate intensity treadmill training slows tumor growth in a mouse model of pancreatic cancer. The mechanisms by which tumor growth is reduced are not fully understood. Natural Killer (NK) cells are known to be highly responsive to exercise and have been shown to mediate the beneficial effect of exercise in other cancer types. PURPOSE: We therefore compared NK cell function between pancreatic-tumor bearing mice who completed one of three exercise interventions to sedentary, pancreatic-tumor bearing mice. METHODS: Tumors were induced in male C57Bl/6 mice (6-8 weeks old) via subcutaneous injection of pancreatic ductal adenocarcinoma (PDAC-4662) tumor cells. Once tumors were palpable, mice received gemcitabine treatment (GEM) and began their assigned intervention: high volume exercise (45 min treadmill running at 12 m/min, 5 days/week), low volume exercise (15 min at 12 m/min, 5 days/week), high intensity interval training (20 intervals of 1 min at 20 m/min, followed by 1 min at 8 m/min, 3 days/week), or sedentary (SED). Additional mice were assigned to each exercise group but did not receive GEM. After two weeks, and 24-48 hours post-exercise, mice were euthanized and spleens extracted and digested. NK cell function was measured following stimulation with PDAC-4662 cells with a CD107a degranulation assay and detected by flow cytometry. Group differences in NK cell degranulation were assessed by one-way ANOVA. RESULTS: In GEM treated mice, there were no differences in NK cell cytotoxicity against PDAC4662 tumor cells amongst any of the groups (F(3,14) =1.823; p = 0.201, η2 = 0.332). Similarly, mice not treated with GEM did not exhibit group-differences in NK cell cytotoxicity (F(3,16) =0.714; p = 0.561, η2 = 0.141). CONCLUSIONS: Two weeks of exercise training did not yield differences in NK cell function in pancreatic tumor bearing mice. It may be that a longer duration intervention is needed to impact NK cell function. Exercise after two weeks was not possible due to tumor-related morbidity; thus beginning the intervention earlier in tumor development should be considered. Supported by American College of Sports Medicine Research Foundation