Physical activity delays accumulation of immunosuppressive myeloid-derived suppressor cells

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, w...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2020-06, Vol.15 (6), p.e0234548-e0234548
Main Authors: Garritson, Jacob, Krynski, Luke, Haverbeck, Lea, Haughian, James M, Pullen, Nicholas A, Hayward, Reid
Format: Article
Language:English
Subjects:
Accumulation
Anticancer properties
Biology and Life Sciences
Biomarkers
Blood
Bone marrow
Bone marrow cells
Breast cancer
Cancer metastasis
Carcinoma
Care and treatment
CD3 antigen
CD4 antigen
Cell proliferation
Cytokines
Cytotoxicity
Exercise
Flow cytometry
Health aspects
Immune response
Immunosuppressive agents
Immunotherapy
Injection
Lung nodules
Lymphocytes
Lymphocytes T
Mammary gland
Medicine and Health Sciences
Metastases
Myeloid cells
Nodules
Physical activity
Physical fitness
Physiological aspects
Prevention
Rehabilitation
Research and Analysis Methods
Spleen
Studies
Suppressor cells
Suppressors
Tumors
Wheel running
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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.sup.+ CD4.sup.+ 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. These findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0234548