Research has shown that the immune system doesn’t function properly in patients with multiple myeloma, a blood cancer that occurs when plasma cells — a type of white blood cell — multiply out of control. But a clinical trial led by Jens Hillengass, MD, PhD, Chief of Myeloma at Roswell Park Comprehensive Cancer Center, shows that exercise may have the power to strengthen the immune system in those patients, providing a nonpharmaceutical method of helping control the disease.
The results of that trial were shared earlier this summer, “T cell exhaustion is lower after a physical activity intervention in multiple myeloma patients,” at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The work will be presented by first author Janine Joseph, MS, MBA, pre-doctoral trainee and Senior Research Specialist in the Department of Cancer Prevention and Control at Roswell Park, as part of a session on Hematologic Malignancies — Plasma Cell Dyscrasia.
“With these encouraging results from our pilot study, we have been able to show for the first time in myeloma patients that the immune system can be influenced by lifestyle interventions like supervised exercises,” says Dr. Hillengass, senior author on the study. “We have therefore started a larger prospective trial offering remote supervised exercise or intermittent fasting to influence parameters such as immune function, bone disease and microbiome in patients with monoclonal plasma cell disorders.”
The study focuses on CD4+ and CD8+ T cells — white blood cells that are part of the immune system and capable of fighting cancer. When those cells are exhausted, they become too weak to sustain the attack. While preclinical studies have shown that exercise can reduce immune exhaustion, few studies have examined how exercise affects biomarkers that measure immune exhaustion in cancer patients, especially those with multiple myeloma.
The research team looked at two biomarkers of T cell exhaustion: TIGIT, an immune inhibitory receptor that can reduce the effectiveness of T cells and prevent them from multiplying, and PD-1, which can exhaust T cells and suppress the immune system. The Roswell Park team measured the ratio of exhausted CD4+ and CD8+ T cells – those that expressed either marker – to non-exhausted CD4+ and CD8+ T cells, comparing this ratio before and after the exercise regimen.
The clinical trial enrolled 43 patients, who took part in a six-month program of physical activity. Approximately half the group received supervised strength training twice a week, while the other half, unsupervised, used activity trackers with remote prompts to gradually increase their walking. Participants provided blood samples before and after the exercise intervention to provide a comparison of the number of exhausted vs. non-exhausted T cells. Twenty-four participants completed the intervention and provided blood samples at two time points.
The research team used flow cytometry, a technique used to identify cell properties, to determine how many exhausted and non-exhausted T cells participants had before and after the intervention. At the end of the six-month exercise intervention, they found that the typical participant had a less-exhausted T-cell profile than at baseline. Specifically, the ratio of CD4+ TIGIT+ to non-exhausted CD4+ cells was reduced significantly, from 0.71 to 0.57. The ratio of CD8+ PD-1+ to non-exhausted CD8+ cells was somewhat reduced, from 1.81 to 1.48. These data suggest that physical activity can affect the immune systems of patients with multiple myeloma, creating an environment with fewer exhausted T cells and more robust T cells capable of fighting the cancer.
“We were excited by the outcome of this study, because it suggested that our patients might be able to achieve a less-exhausted immune system through exercise, which comes with many other health and quality-of-life benefits,” says Joseph. “There’s a lot more work to be done, but we’re hoping this study lays the groundwork for a better understanding of whether exercise should be recommended to myeloma patients to improve their immune function.”
That effort is already underway. The clinical trial, “Non-chemotherapeutic interventions for the improvement of quality of life and immune function in patients with multiple myeloma” (NCT05312255), has a targeted enrollment of 150 patients.
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