Integrated mechanisms and clinical relevance of exercise driven remodeling of the tumor immune microenvironment

Immunotherapy has transformed cancer treatment, yet its overall efficacy remains constrained because the immune environment surrounding tumors is frequently maintained in a chronically suppressed state. A substantial body of epidemiological and clinical evidence indicates that regular physical activity is consistently associated with reduced cancer incidence, lower recurrence rates, and prolonged survival. Despite these observations, the underlying biological basis has not been systematically clarified. Current data suggest that exercise modulates the immune environment through coordinated systemic and local pathways. At the systemic level, exercise mobilizes and activates immune cells while reducing chronic inflammation and physiological stress, thereby establishing conditions that favor immune responsiveness. At the local level, exercise improves blood supply, tissue architecture, and metabolic conditions within tumors and reshapes immune cell composition, collectively enhancing immune recognition and clearance of malignant cells. The concept of an immune plasticity window describes the capacity of the immune environment to transition from a suppressed to a responsive state and provides a unifying framework to integrate the diverse immunological effects of exercise. This framework helps explain interindividual variability in responses to exercise interventions and offers a conceptual basis for incorporating exercise into comprehensive cancer treatment strategies. By synthesizing clinical associations with mechanistic insights, this review emphasizes that exercise acts by globally improving the immune environment rather than targeting isolated pathways, supporting its potential role as an adjunct intervention to enhance therapeutic efficacy and long-term outcomes.