Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy

Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer development. We further delineate the effects of exercise on immune cell function, demonstrating its potential to mitigate immunosenescence and enhance antitumor responses. We also discuss the implications of immunosenescence for the efficacy of immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapy, and explore the potential benefits of combining exercise with these interventions. Collectively, this review underscores the importance of understanding the complex relationship between immunosenescence, physical exercise, and antitumor immunity, paving the way for the development of innovative strategies to improve cancer outcomes in the aging population.