Physical activity delays accumulation of immunosuppressive myeloid-derived suppressor cells

Abstract

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 posttumor 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

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy

“…In agreement with another animal breast cancer model, wheel running after the establishment of breast cancer limited the accumulation of MDSCs. 78 Since both polymorphonuclear MDSCs, monocytic MDSCs, and other immunosuppressive myeloid cells strongly negate responses to cancer immunotherapy, [79][80][81] exercise may improve immune responses to checkpoint blockade by limiting the effects of these cells. It should be noted that it appears that inactivity and/or obesity may have an opposite effect on the response to checkpoint blockade.…”

Intermittent fasting suppressed splenic CD205+ G‐MDSC accumulation in a murine breast cancer model by attenuating cell trafficking and inducing apoptosis

“…MDCSs have also been implicated in nonimmunological functions, such as promoting angiogenetic tumor cell invasion and metastasis (Priceman et al., 2010 ; Yang et al., 2004 , 2008 ). Accordingly, MDSCs are broadly viewed as a crucial factor attenuating the efficacy of some cancer immunotherapies, and thus, any interventive strategy that minimizes the negative influence of MDSCs may significantly improve outcomes for patients treated with immunotherapies (Ding et al., 2014 ; Garritson et al., 2020 ; Highfill et al., 2014 ).…”

The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration

“…While this model has its challenges because the mice could wheel run ad libitum, there was a beneficial effect of exercise, and it was dependent on IL-6 (presumably muscle-derived) and epinephrine [ 152 ]. A similar study using a breast cancer mouse model supports this immune-potentiating effect by showing that exercise reduced myeloid-derived suppressor development [ 153 ].…”