Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer.

Background: Reduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls. Methods: Age-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise. Results: At 0 h, conventional T cell counts increased by 45%-64% with no differences between groups. T cell frequency decreased by -3.5% for CD3+ and -4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of -4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was -18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h. Conclusion: Following acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

Feasibility of home-based exercise training in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Home-based training increases accessibility to exercise and mitigates the side effects of hormone therapy for prostate cancer (PC). However, it is unknown if men with more advanced disease are willing to partake in such interventions. PURPOSE: To determine the feasibility of a home-based exercise intervention in men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: mCRPC patients on androgen receptor signaling inhibitors (ARSI) were prescribed a 12-week, home-based exercise intervention using resistance bands and walking. Feasibility was assessed using recruitment, retention, adherence, and outcome capture. Physiological changes and patient reported outcomes were assessed before and after the intervention. RESULTS: Of the 62 referrals, 47 were eligible with 22 men performing baseline testing (47% recruitment rate) and 16 completing the intervention (73% retention). Task completion was >86% for all physiological tests. Walking adherence was 80% and resistance training was 63%, the latter falling short of the study target (75%). Training increased thigh muscle cross-sectional area by 22%, time to exhaustion by 19% (both p < 0.05) and peak oxygen uptake by 6% (p = 0.057). Improvements in short physical performance battery scores and 400 m walk demonstrated moderate effect sizes that did not reach significance. CONCLUSIONS: Home-based exercise is feasible during ARSI treatment for mCRPC. Greater endurance capacity and localized hypertrophy appear as the primary improvements following training. These preliminary findings suggest home-based training may increase exercise accessibility, with important lessons that will inform subsequent trials investigating the efficacy of home-based exercise interventions during mCRPC.

Impact of community-based exercise on fatigue in early breast cancer survivors: identifying potential determinants of change.

BACKGROUND: Exercise has been shown to reduce fatigue in early breast cancer survivors (EBCS), though it is unclear if these results translate to community-based exercise settings. Mechanisms that influence changes in fatigue seen after exercise are also poorly understood. This study sought to evaluate the impact of community-based exercise and identify associations of fatigue in EBCS. METHODS: Twenty-nine EBCS and 13 non-cancer controls (CON) enrolled. Pre/post-intervention measurements included measures of fitness/function, balance, and adherence/compliance as well as self-reported measures of fatigue, health-related quality of life (HRQOL), well-being, self-efficacy, and physical activity. Both groups participated in a supervised 16-week aerobic + resistance exercise intervention. A mixed model ANOVA and Cohen's D effect size assessed fatigue changes, and univariable linear regressions identified fatigue associations. RESULTS: Fatigue improved for EBCS (- 2.6, Cohen's D = 0.51) but not CON (0.0, Cohen's D = 0.02); no interaction effect was observed. Post-intervention fatigue in EBCS was associated with better QOL (R2 = 0.387; p < 0.01), depression (R2 = 0.251; p < 0.01), self-efficacy, (R2 = 0.453; p < 0.01), outcome expectations from exercise (R2 = 0.254; p < 0.01), balance (R2 = 0.167; p < 0.05), and the 6-minute walk test (R2 = 0.193; p < 0.05). EBCS improvements in fatigue were associated with improvements in self-reported physical health (R2 = 0.425; p < 0.01), depression (R2 = 0.233; p < 0.01), pain (R2 = 0.157; p < 0.05), outcome expectations from exercise (R2 = 0.420; p < 0.01), and the 6-minute walk test (R2 = 0.172; p < 0.05). Less fatigue in the CON group was shown be associated with better sleep quality (R2 = 0.309; p < 0.05) and pain (R2 = 0.259; p < 0.05). CONCLUSION: Community-based exercise appears beneficial for alleviating fatigue in EBCS. These improvements may be driven by parallel improvements in psychosocial outcomes and objectively measured functional outcomes.

Baseline fatigue in early breast cancer survivors: understanding its prevalence in community-based exercise.

PURPOSE: Examine baseline fatigue levels in early-breast cancer survivors (EBCS) compared to inactive controls (CON) and identify associated physical and psychosocial factors with fatigue prior to community-based exercise. METHODS: A total of 33 EBCS (53.9 ± 11.4 years) and 21 CON (54.0 ± 8.0 years) were recruited. Participants completed questionnaires for demographics and patient-reported outcome measures pertaining to fatigue, quality of life, mental health, and physical activity, and completed a 6-min walk test, balance assessment, cardiopulmonary exercise test (VO2peak), and muscular strength test. A Mann-Whitney U test compared fatigue between groups and unadjusted univariable linear regressions were used to explore relationships with fatigue. RESULTS: Fatigue in EBCS was not statistically different from CON (EBCS: 16.9 ± 5.75; CON: 14.2 ± 3.4, p = 0.121). Univariable analyses showed lower fatigue in EBCS was associated with better Physical and Mental Health (both R2 = 0.435; p < 0.01), better outcome expectations for exercise (R2 = 0.237; p < 0.01), better self-efficacy (R2 = 0.407; p < 0.01), lower depression (R2 = 0.383; p < 0.001), lower anxiety (R2 = 0.104; p < 0.05), and better balance (R2 = 0.265; p < 0.01). Lower fatigue in the CON group was associated with better sleep quality (R2 = 0.263; p < 0.05) and self-efficacy (R2 = 0.417; p < 0.05). CONCLUSIONS: Mild fatigue was prevalent in EBCS, whereas moderate/severe fatigue was not. This discrepancy should be explored provided the benefits of exercise for fatigue management. Further, fatigue in EBCS was associated with multiple psychosocial and functional outcomes, which emphasized both its multi-factorial nature and uniqueness to the EBCS population. CLINICALTRIALS: gov Number: NCT03760536.

Physical Activity Can Enhance Life (PACE-Life): results from a 10-week walking intervention for individuals with schizophrenia spectrum disorders.

BACKGROUND: Premature mortality in individuals with schizophrenia spectrum disorders (SSDs) is largely due to high rates of chronic health conditions. Although exercise has been shown to improve health in this population, scalable and accessible interventions are limited. AIM: To examine the impact of Physical Activity Can Enhance Life (PACE-Life), a novel walking intervention, on physical activity, and on secondary outcomes of cardiorespiratory fitness (CRF), physical health, autonomous motivation, social support, and quality of life. METHOD: Sixteen individuals with SSDs were enrolled in a 10-week open trial. The intervention included walking groups, home-based walks, Fitbit use, and goal-setting and if-then plans. Within-group effect sizes were calculated to represent changes from baseline to post-test and 1-month follow-up. RESULTS: Participants increased self-reported weekly walking minutes and decreased daily hours spent sitting; however, Fitbit-recorded exercise behavior changed only minimally. There were also improvements in secondary outcomes including autonomous motivation and hip circumference. CRF improved only minimally, and findings were relatively unchanged with outliers removed from the full sample. CONCLUSIONS: This open trial demonstrates modest improvements in key parameters of exercise behavior and physical health from participating in PACE-Life. Future research should assess the efficacy of this intervention in a randomized controlled trial.

The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors.

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03760536.

Exercise-induced modulation of monocytes in breast cancer survivors.

BACKGROUND: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. OBJECTIVES: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. METHODS: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. RESULTS: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß+CD14+CD16+ MFI (-11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (-63, p=0.002) and CD14+CD16+ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. CONCLUSIONS: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Impact of community-based exercise program participation on aerobic capacity in women with and without breast cancer.

BACKGROUND: Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM: To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS: A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS: The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION: Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Exercise training partially rescues impaired mucosal associated invariant t-cell mobilization in breast cancer survivors compared to healthy older women.

Exercise may attenuate immunosenescence with aging that appears to be accelerated following breast cancer treatment, although limited data on specific cell types exists and acute and chronic exercise have been investigated independently in older adults. PURPOSE: To determine the mucosal associated invariant T (MAIT) cell response to acute exercise before (PRE) and after (POST) 16 weeks of exercise training in breast cancer survivors (BCS) and healthy older women (CON). METHODS: Age-matched BCS and CON performed 45 min of intermittent cycling at 60% peak power output wattage. Blood samples were obtained at rest, immediately (0 h) and 1 h after exercise to determine MAIT cell counts, frequency, and intracellular cytokine expression. RESULTS: At PRE, MAIT cell counts were greater in CON (137%) than BCS at 0 h (46%, p < 0.001), with increased MAIT cell frequency in CON but not BCS. TNFα+ and IFNγ+ MAIT cell counts increased at 0 h by ~120% in CON (p < 0.001), while BCS counts and frequencies were unchanged. Similar deficits were observed in CD3+ and CD3+ CD8+ cells. At POST, exercise-induced mobilization and egress of MAIT cell counts and frequency showed trends towards improvement in BCS that approached levels in CON. Independent of group, TNFα frequency trended to improve (p = 0.053). CONCLUSIONS: MAIT mobilization in older BCS following acute exercise was attenuated; however, exercise training may partially rescue these initial deficits, including greater sensitivity to mitogenic stimulation. Using acute exercise before and after interventions provides a unique approach to identify age- and cancer-related immuno-dysfunction that is less apparent at rest.

Community-based exercise programs and cancer-related fatigue: a systematic review and meta-analysis.

PURPOSE: To explore the prevalence of cancer-related fatigue (CRF) within community-based exercise programs and to determine the overall impact that participation in community-based exercise programs have on CRF. METHODS: Literature searches were performed in March and updated in April of 2020. Studies that were community-based in adult cancer populations and reported CRF outcomes were included. Mean and standard deviations for CRF from 12 studies were extracted in order to compute a pooled effect size via a random effects model. An overall percentage was computed to discern how many community-based exercise programs reported CRF. RESULTS: Sample sizes varied among studies with most patients being middle-aged with breast cancer in the post-treatment setting. Most programs implemented aerobic + resistance exercise training interventions (~77%). Only ~42% of programs identified in the review reported CRF outcomes. The random effects model produced a pooled effect size of 0.30 (p < 0.001). CONCLUSIONS: Fewer than half of the identified community-based exercise programs reported CRF outcomes (~42%). Of those that did, the random effects model revealed a small yet significant impact on improving CRF after exercise participation, though more research is certainly needed in this area. This review produced promising preliminary evidence for the impact of community-based exercise programs on CRF. As exercise interventions transition to community-based facilities, patients should feel confident that these programs will continue to assist in managing CRF that is commonly experienced across the cancer continuum.