Physical activity delays accumulation of immunosuppressive myeloid-derived suppressor cells.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are potent suppressors of immune function and may play a key role in the development and progression of metastatic cancers. Aerobic exercise has been shown to have anticancer effects, yet the mechanisms behind this protection are largely unknown. Therefore, we examined the effects of physical activity on MDSC accumulation and function. METHODS: Female BALB/c mice were assigned to one of two primary groups: sedentary tumor (SED+TUM) or wheel run tumor (WR+TUM). After 6 weeks of voluntary wheel running, all animals were randomly subdivided into 4 different timepoint groups; 16, 20, 24, and 28 days post-tumor injection. All mice were inoculated with 4T1 mammary carcinoma cells in the mammary fat pad and WR groups continued to run for the specified time post-injection. Spleen, blood, and tumor samples were analyzed using flow cytometry to assess proportions of MDSCs. RESULTS: Cells expressing MDSC biomarkers were detected in the spleen, blood, and tumor beginning at d16. However, since there was no evidence of immunosuppressive function until d28, we refer to them as immature myeloid cells (IMCs). Compared to SED+TUM, levels of IMCs in the spleen were significantly lower (p < 0.05) in WR+TUM at day 16 (33.0 ± 5.2%; 23.1 ± 10.2% of total cells, respectively) and day 20 (33.9 ± 8.1%; 24.3 ± 5.1% of total cells, respectively). Additionally, there were fewer circulating IMCs in WR+TUM at day 16 and MDSC levels were significantly lower (p < 0.05) in the tumor at day 28 in WR+TUM. Additionally, a non-significant 62% and 26% reduction in metastatic lung nodules was observed at days 24 and 28, respectively. At day 28, MDSCs harvested from SED+TUM significantly suppressed CD3+CD4+ T cell proliferation (3.2 ± 1.3 proliferation index) while proliferation in WR+TUM MDSC co-cultures (5.1 ± 1.7 proliferation index) was not different from controls. CONCLUSIONS: These findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies.

Validity of a customized submaximal treadmill protocol for determining VO2max.

INTRODUCTION: A customized submaximal exercise test for cycle ergometry was reported as a superior estimate of maximum oxygen uptake (VO2max) in comparison to the traditional YMCA ergometry test. PURPOSE: Following similar methodology, we sought to validate a customized submaximal treadmill test (CustomTM) compared with the widely used Bruce submaximal protocol. METHODS: Participants (29 women and 21 men; age = 31.37 ± 11.44 year, BMI = 24.02 ± 3.03) performed a graded exercise test (GXT) with a subsequent exhaustive, square-wave bout for the verification of "true" VO2max. In counterbalanced order, subjects then completed submaximal protocols. The CustomTM protocol consisted of two 3-min stages estimated at 35 and 70% of VO2max, where VO2max was estimated with a linear regression equation utilizing sex, BMI, age, and self-reported physical activity. RESULTS: VO2 values from the GXT and verification bout were 47.2 ± 7.7 and 47.0 ± 7.7 ml kg-1 min-1, respectively (ICC = 0.99, CV = 2.0%, TE = 0.83 ml kg-1 min-1), with the highest value used as "true" VO2max (47.7 ± 7.7 ml kg-1 min-1). Neither the Bruce (45.95 ± 6.97 ml kg-1 min-1) nor the CustomTM (47.3 ± 9.4 ml kg-1 min-1) protocol differed from "true" VO2max. The CustomTM had a "very large" measurement agreement with "true" VO2max (ICC = 0.78, CV of 9.1%, TE = 4.07 ml kg-1 min-1). Bruce had a "large" measurement agreement with "true" VO2max (ICC = 0.62, CV of 10.0%, TE = 4.51 ml kg-1 min-1). CONCLUSION: The CustomTM was superior to the Bruce protocol, because it included a stage below and above gas exchange threshold, yielded a better measurement agreement for "true" VO2max, and was more time efficient.