Aging modulation of the immune system and immunotherapy efficacy in cancer

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactions and other mediators serve as critical links connecting aging and cancer, exerting complex anti-tumor and pro-tumor effects. However, in the context of immunosenescence, these factors collectively contribute to the formation of an immunosuppressive tumor microenvironment (TME) that facilitates tumor immune evasion and proliferation. Clinical data reveal that immunotherapy in older adults is often challenged by variable treatment efficacy and reduced tolerance. This review systematically summarizes the data related to elderly patients in immunotherapy for different types of cancers, and discusses potential immunotherapy sensitization strategies tailored for elderly patients and the mechanisms and immunomodulatory effects of senescence-modulating drugs, with the aim of enhancing therapeutic response rates and improving safety profiles.