REACT - REstoring immune function through physical Activity: a translational approaCh to Tumour prevention in the elderly

Abstract:

Aging is associated with immunosenescence and chronic low-grade inflammation, both of which significantly increase cancer susceptibility. Among immune effectors, CD8⁺ T cells play a critical role in tumour surveillance; however, in the elderly, their function is compromised by metabolic exhaustion- parricularly mitochondrial dysfunction- leading to impaired antitumor immunity and poor outcomes. Emerging evidence suggests that aerobic physical activity (PA) may counteract these effects by restoring CD8⁺ T cell functionality and reinforcing cytotoxic responses.

This study investigates the capacity of structured PA to reprogram CD8⁺ T cell metabolism and function in both young and elderly individuals. Through longitudinal sampling (peripheral blood mononuclear cells, plasma, and sera) and advanced immunometabolic profiling—including SCENITH and in vitro priming of EV10-specific CD8+ T cells— the bioenergetic fitness, cytotoxic potential, immunometabolic resilience of CD8⁺ T cells and their tumour surveillancecapacity.in physical active versus sedentary cohorts over 6 to 36 months, will be assessed.

Additionally, circulating biomarkers and microRNAs (e.g. miR-21, let-7 family, CXCL10) will be analysed as minimally invasive indicators of PA-induced immune modulation. These biomarkers may serve as predictive tools for cancer prevention strategies and personalized health monitoring. By bridging basic immunology, exercise physiology, and translational medicine, REACT aims to deliver actionable insights into how lifestyle interventions can mitigate age-related cancer risk. Findings may inform public health policies and contribute to reduce healthcare costs, promoting healthy aging through immune resilience.