Patient stratification in exercise oncology: matching exercise modalities to immune phenotypes to optimize...

Despite advances in oncology, the clinical response to treatments, particularly immunotherapy, remains highly variable due to the complex tumor immune microenvironment. While regular exercise is recognized as a supportive intervention to improve patient outcomes, its mechanistic integration into personalized cancer care is limited by a generalized approach to physical activity. In this review, we argue that the heterogeneity of exercise benefits stems from modality-specific immune remodeling. Evidence indicates that distinct exercise types elicit specific "immune stimulation fingerprints". Steady-state aerobic exercise primarily resolves chronic inflammation and promotes immune homeostasis; resistance training preserves the muscle-immune axis, providing critical physical and immune reserves to maintain treatment tolerance; and high-intensity interval training can provoke acute mobilization of effector immune cells. Importantly, the ability of these systemic immune adaptations to enhance treatment response depends heavily on the local tumor immune niche. To bridge the gap between systemic exercise effects and clinical outcomes, we propose the "exercise-immune matching window" model. This framework highlights that improving therapeutic efficacy-and potentially optimizing responses to immunotherapy-requires patient stratification. By aligning specific exercise modalities with the individual's baseline immunophenotype (e.g., chronic inflammation, significant immunosuppression, or immunosenescence) and treatment stage, we can maximize synergistic effects. Ultimately, transitioning from generic exercise recommendations to tailored, immune-directed prescriptions offers a practical strategy to augment comprehensive cancer management.