Immunosenescence in lung cancer: Linking aging, chronic inflammation, and tumor immune dysfunction

Lung cancer is predominantly diagnosed in older adults, raising important questions regarding the contribution of age-related biological changes to tumor development and immune regulation. Aging is accompanied by progressive remodeling of the immune and pulmonary systems, including immunosenescence, cellular senescence, inflammaging, metabolic alterations, and changes in tissue homeostasis. However, the extent to which these interconnected processes contribute to impaired antitumor immunity and shape the tumor microenvironment remains incompletely understood. In particular, chronological age does not necessarily reflect the functional state of antitumor immunity, and the biological basis for heterogeneity in immune function and immunotherapy response among older individuals requires further clarification. This issue has become increasingly relevant with the expanding use of immune checkpoint inhibitors in lung cancer and growing interest in biological and immunological measures of aging. In this narrative review, the age-associated remodeling of the pulmonary and immune systems is examined through an integrated perspective linking immunosenescence, cellular senescence, and inflammaging to tumor immune dysfunction. Age-related alterations in T cells, natural killer cells, antigen-presenting cells, macrophages, and the senescent-cell secretory environment are considered in relation to impaired immune surveillance, chronic inflammation, immune escape, and therapeutic response. Emerging approaches targeting senescent cells, metabolic and mitochondrial dysfunction, the aging tumor microenvironment, and immune-cell function are also discussed. By integrating these interconnected dimensions of immune aging, this review provides a framework for understanding why chronological age alone may be insufficient to characterize antitumor immune competence and highlights the potential value of biologically informed approaches to cancer prevention and treatment. This perspective may help guide future research toward more precise assessment of immune aging and individualized therapeutic strategies.