Immunosenescence in elderly patients with advanced non-small cell lung cancer: Mechanisms and therapeutic implications

Non-small cell lung cancer (NSCLC) remains the most prevalent malignancy worldwide and is a leading cause of cancer-related mortality, particularly among older adults. The global demographic shift towards an aging population underscores the critical role of immunosenescence as a pivotal factor influencing NSCLC pathogenesis, progression, and response to immunotherapy. Immunosenescence, defined by the progressive decline in immune system function with advancing age, is characterized by quantitative and qualitative changes in immune cells. These changes include thymic involution, T-cell exhaustion, epigenetic modifications, reduced immune responsiveness, and a chronic low-grade inflammatory state. This review aims to integrate the current understanding of the biomarkers, molecular mechanisms, and genetic factors underlying immunosenescence. Additionally, it critically examines how immunosenescence affects tumor immune surveillance and the tumor microenvironment (TME). By synthesizing these insights, we aim to inform the development of targeted therapeutic strategies for advanced NSCLC in elderly patients, ultimately enhancing treatment efficacy and patient outcomes.