Treadmill and T Cells: Can Exercise Enhance Immune Responses in Breast Cancer?
Posted: Tuesday, May 11, 2021
Aerobic exercise may decrease tumor growth and reprogram the breast cancer tumor microenvironment by increasing pericyte coverage and perfusion and decreasing hypoxia, according to preclinical mouse-model study results reported in Cancer Immunology Research. The work provides clues to the biologic basis behind the connection between exercise and increased antitumor immune response, with potential therapeutic implications for patients with breast cancer. The study was conducted by Dai Fukumura, MD, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues.
The most exciting finding, Dr. Fukumura said in a Massachusetts General Hospital press release, is that exercise training increased the presence in tumors of activated cytotoxic T lymphocytes (CD8-positive T cells). The CD8-positive T-cell insights also provide possible answers for why immune checkpoint inhibitors have not worked as well against breast cancer as they have against other cancers. Resistance to immune checkpoint blockade can be caused by lack of perfusion, tumoral hypoxia, and T-cell exclusion. The researchers explained how to offset these factors, thus sensitizing tumors to immune checkpoint blockade, have been eagerly sought. In the mice, exercise training accomplished this.
“Exercise training increases CD8-positive T cells by reprogramming the tumor microenvironment toward a less aggressive phenotype, but a large fraction of CD8-positive T cells remain expressing immune checkpoint receptors, suggesting these tumors would benefit from immune checkpoint blockade therapy,” the scientists continued. However, the team also discovered that without the chemokines CXCL9 and CXCL11—which were genetically engineered out of some mice—CD8-positive T cells were not recruited to the tumors the malignancies grew at the same rate whether the mice exercised or not. Thus, the CXCL9/CXCL11-CXCR3 pathway remains an integral piece of the puzzle.
“Supervised exercise training has the potential to unleash antitumor response from immunotherapy,” declared the team. “Rewired tumor immunity” was accomplished with daily 30- to 45-minute sessions of continuous, moderate-to-vigorous aerobic exercise.
Disclosure: The study authors’ disclosure information can be found at cancerimmunolres.aacrjournals.org.