Healthy lifestyle interventions for childhood and adolescent cancer survivors: a systematic review and meta-analysis.

PURPOSE: This study investigated the effects of healthy lifestyle interventions (HLSIs) on health-related quality of life (HR-QoL) in childhood and adolescent cancer survivors (CACS). METHODS: Major databases were searched for English-language original articles published between January 1, 2000 and May 2, 2021. Randomized controlled trials (RCTs) and non-RCTs were included. Quality was assessed using the revised Cochrane risk-of-bias tool, and a meta-analysis was conducted using RevMan 5.3 software. RESULTS: Nineteen studies were included. Significant effects on HR-QoL were found for interventions using a multi-modal approach (exercise and education) (d=-0.46; 95% confidence interval [CI]=-0.84 to -0.07, p=.02), lasting not less than 6 months (d=-0.72; 95% CI=-1.15 to -0.29, p=.0010), and using a group approach (d=-0.46; 95% CI=-0.85 to -0.06, p=.02). Self-efficacy showed significant effects when HLSIs provided health education only (d=-0.55; 95% CI=-0.92 to -0.18; p=.003), lasted for less than 6 months (d=-0.40; 95% CI=-0.69 to -0.11, p=.006), and were conducted individually (d=-0.55; 95% CI=-0.92 to -0.18, p=.003). The physical outcomes (physical activity, fatigue, exercise capacity-VO2, exercise capacity-upper body, body mass index) revealed no statistical significance. CONCLUSION: Areas of HLSIs for CACS requiring further study were identified, and needs and directions of research for holistic health management were suggested.

Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and ß-Catenin Signaling.

Retrospective observational studies have reported that statins improve clinical outcomes in patients previously treated with programmed cell death protein 1 (PD-1)-targeting monoclonal antibodies for malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC). In multiple mouse cancer models, de novo synthesis of mevalonate and cholesterol inhibitors was found to synergize with anti-PD-1 antibody therapy. In the present study, we investigated whether statins affect programmed death-ligand 1 (PD-L1) expression in cancer cells. Four statins, namely simvastatin, atorvastatin, lovastatin, and fluvastatin, decreased PD-L1 expression in melanoma and lung cancer cells. In addition, we found that AKT and ß-catenin signaling involved PD-L1 suppression by statins. Our cellular and molecular studies provide inspiring evidence for extending the clinical evaluation of statins for use in combination with immune checkpoint inhibitor-based cancer therapy.