Physical activity delays accumulation of immunosuppressive myeloid-derived suppressor cells
| Autor: | Luke M. Krynski, Jacob Garritson, Nicholas Pullen, James M. Haughian, Lea Haverbeck, Reid Hayward |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proliferation index Physiology medicine.medical_treatment Lymphocyte Activation Lung and Intrathoracic Tumors Running Mice White Blood Cells 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences Myeloid Cells Public and Occupational Health Multidisciplinary medicine.diagnostic_test biology T Cells Immunosuppression Animal Models Body Fluids Blood medicine.anatomical_structure Experimental Organism Systems Oncology 030220 oncology & carcinogenesis Medicine Female Cellular Types Anatomy Immunosuppressive Agents Research Article medicine.medical_specialty Immune Cells Science CD3 T cell Immunology Mouse Models Bone Marrow Cells Spleen Motor Activity Research and Analysis Methods Flow cytometry 03 medical and health sciences Model Organisms Immune system Cell Line Tumor Internal medicine medicine Animals Cell Proliferation Immunosuppression Therapy Blood Cells Biological Locomotion Myeloid-Derived Suppressor Cells Mammary Neoplasms Experimental Biology and Life Sciences Cancers and Neoplasms Physical Activity Cell Biology Coculture Techniques 030104 developmental biology Endocrinology Animal Studies biology.protein Myeloid-derived Suppressor Cell |
| Zdroj: | PLoS ONE, Vol 15, Iss 6, p e0234548 (2020) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0234548 |
| Popis: | BackgroundMyeloid-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.MethodsFemale 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.ResultsCells 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.ConclusionsThese findings suggest that physical activity may delay the accumulation of immunosuppressive MDSCs providing a broader window of opportunity for interventions with immunotherapies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|