Voluntary wheel running can lead to modulation of immune checkpoint molecule expression.

BACKGROUND: Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy. MATERIAL AND METHODS: The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors. RESULTS: Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels. CONCLUSION: B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.

Every exercise bout matters: linking systemic exercise responses to breast cancer control.

Cumulative epidemiological evidence shows that regular exercise lowers the risk of developing breast cancer and decreases the risk of disease recurrence. The causality underlying this relation has not been fully established, and the exercise recommendations for breast cancer patients follow the general physical activity guidelines, prescribing 150 min of exercise per week. Thus, elucidations of the causal mechanisms are important to prescribe and implement the most optimal training regimen in breast cancer prevention and treatment. The prevailing hypothesis on the positive association within exercise oncology has focused on lowering of the basal systemic levels of cancer risk factors with exercise training. However, another rather overlooked systemic exercise response is the marked acute increases in several potential anti-cancer components during each acute exercise bout. Here, we review the evidence of the exercise-mediated changes in systemic components with the ability to influence breast cancer progression. In the first part, we focus on systemic risk factors for breast cancer, i.e., sex hormones, insulin, and inflammatory markers, and their adaptation to long-term training. In the second part, we describe the systemic factors induced acutely during exercise, including catecholamines and myokines. In conclusion, we propose that the transient increases in exercise factors during acute exercise appear to be mediating the positive effect of regular exercise on breast cancer progression.

Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity.

To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.