Want to catch up with the other articles in this series?
Part 1: What is the impact of endurance training on human lifespan?
Part 1.1: What is VO2max?
Part 2: What are training zones?
Part 2.1: How do muscle fiber types correspond to training zones?
Part 2.2: Training zones 1, 2 and 3
Part 2.3: Training zones 3, 4, 5 and 6
Part 2.4: Moderate intensity vs. high intensity exercise
Part 3: By which mechanisms does exercise delay aging and prevent chronic disease?
Part 3.1: What are the cardiovascular adaptations to endurance training?
Part 3.2: What are the metabolic adaptations to endurance training?
Part 3.3: Can exercise prevent or even treat cancer?
Part 3.4: How does exercise impact the immune system?
Part 3.5: Exercise as a therapy for neurodegeneration and conclusions
Impact of exercise on the immune system with a focus on haematological cancer
Exercise and T-cell Function
Exercise and physical activity have been shown to have immunomodulatory effects in hematologic cancers, specifically in terms of T cells. T cells play a crucial role in the immune system and their dysfunction is common in hematologic malignancies, which can be further worsened by chemotherapy. Exercise has been shown to improve T-cell function and reduce immunosenescence, a process associated with increased mortality risk. Studies have demonstrated that exercise can improve T-cell phenotype and function, as well as increase the cytotoxic activity of T cells towards tumour antigens. These findings suggest that exercise may be a useful adjunctive therapy to improve T-cell function and potentially improve outcomes in hematologic cancers.
In a study comparing older adults (aged 55-79 years) who were either sedentary or “master athletes” (men with the ability to cycle 100 km in 6.5 hours or women with the ability to cycle 60 km in 5.5 hours), immunosenescence was reduced in the master athlete group.
Specifically, master athletes had higher numbers of naive CD4 1 T-cell and recent T-cell thymic emigrants, suggestive of improved thymic and T-cell functions. Furthermore, immune composition of T cells for master athletes was similar to those of young (aged 20-36 years) healthy adults.
Natural killer cells
Natural killer (NK) cells are important immune cells that recognize and kill cancer cells, and their activation and modulation have been shown to be effective in cancer immunotherapy. Defects in NK cell cytotoxicity are common in hematologic malignancies and in individuals at higher risk of cancer, such as the elderly. Hematologic cancer drugs, such as lenalidomide and pomalidomide, can induce NK cell proliferation and enhance NK-mediated cytotoxicity. Exercise has also been shown to improve NK cell function and increase their antitumor properties in both healthy individuals and cancer survivors. Exercise has been associated with increased numbers and altered composition of NK cells in the blood, and increased NK cell cytotoxicity against tumor cell lines. Cross-sectional studies have suggested a positive association between increased aerobic fitness or exercise exposure and NK cell cytotoxicity. Exercise may reconstitute functional NK cells and expose cancer cells to "newer" NK cells that are unaffected by tumor-associated inhibitory mechanisms, potentially improving cancer outcomes.
Older healthy adults (aged 60 years) who engage in at least 10 000 steps per day had better neutrophil pathogen-related chemotactic capacity than age-matched adults who walk only 5000 steps per day.
In younger healthy adults, chemotaxis, phagocytosis, formation of neutrophil extracellular traps, and mitochondrial functions have been improved by either an acute session or weeks of exercise training.
10 weeks of interval exercise training was sufficient to reduce the amount of CD16pos monocytes in healthy adults and older adults with rheumatoid arthritis
Neutrophils
Neutrophils are a type of white blood cell that play a key role in immune defense by phagocytosing and killing pathogens, releasing antimicrobial peptides and cytokines, and forming neutrophil extracellular traps.
Exercise has been shown to improve neutrophil function in older adults and healthy individuals, including increased phagocytosis, chemotaxis, and formation of neutrophil extracellular traps.
Monocytes and macrophages, another type of white blood cell, have been implicated in the progression of hematologic malignancies and are considered a potential target for treatment. Exercise has been associated with altered monocyte/macrophage function, including a reduction in proinflammatory CD16pos monocytes and an increase in the anti-inflammatory M2 subtype.
There is less research on the role of B cells in relation to exercise, but some studies have shown that acute and chronic exercise can alter B cell function and antibody production. Overall, the evidence suggests that exercise may be a useful adjunctive therapy to improve immune cell function and potentially improve outcomes in hematologic cancers.
Clinical trials of exercise as a therapy for hematologic cancers
Clinical trials have explored the potential of exercise as an adjunctive therapy to improve immune cell function and potentially improve outcomes in hematologic cancers. One small study found that an acute session of exercise altered the composition of CD4+ T cells in patients with CLL, with a decrease in pro-tumorigenic regulatory T cells and an increase in T helper 17 cells. Another study found that an acute exercise intervention in patients with NHL led to increased interleukin-6 levels and acetylation of the CD8+ T-cell histone H4K45, suggesting an inflammatory-mediated epigenetic regulatory pathway that could be modified by exercise. A feasibility study in patients with AML undergoing inpatient treatment found significant improvements in cardiorespiratory fitness, fatigue, and depression after 3 to 5 weeks of exercise, but no changes in inflammatory markers. Another study found that an exercise intervention in patients with CLL resulted in increased natural killer cell cytotoxicity and reduced tumor burden in a preclinical model.
Overall, the evidence suggests that exercise may be a promising adjunctive therapy for improving immune cell function in hematologic cancers, but further research is needed to confirm these findings and understand the mechanisms underlying the effects of exercise.
Recommendations for exercise as a therapeutic for cancer
The amount of physical activity is typically measured as the total volume of energy expenditure, or a combination of frequency, intensity, and duration. Epidemiological studies often use metabolic equivalents (METs) to determine intensity, but there are challenges in using meta-analytic techniques to determine the optimal amount and intensity of physical activity associated with lower cancer risk.
The current physical activity guidelines are 150-300 minutes/week of moderate or an equivalent amount of vigorous intensity aerobic activity, but the exact amount needed for reduced risk of cancer is not known. Moderate-vigorous intensity physical activity is associated with reduced risk of many types of cancer, while evidence for light, moderate, or vigorous intensity activity is more limited.
The exact amount of physical activity needed to reduce cancer-specific or all-cause mortality is not yet known as there are limited studies with detailed data on the risk associations for specific doses of activity. However, studies have shown that both absolute levels of pre- and post-diagnosis physical activity are associated with improved survival.
Additionally, data from breast cancer cohort studies suggest that increasing physical activity during the pre-to post-diagnosis period is important for survival outcomes, with an increase in recreational physical activity associated with a 36% lower all-cause mortality risk.
