Special Issue Information

Population aging, a major global trend, is closely intertwined with the biological phenomenon of immunosenescence, together presenting a serious public health challenge. As age advances, the mammalian immune system undergoes progressive functional decline, resulting not only in reduced vaccine efficacy but also in increased susceptibility to infections and a wide range of age-related diseases—particularly malignancies. In cancer therapy, this decline directly contributes to lower response rate of immunotherapy and an increased risk of post-treatment recurrence. This Special Issue aims to provide an in-depth exploration of the complex relationship between immunosenescence and cancer. Aging disrupts both innate and adaptive immune responses: the diversity of T-cell/B-cell repertoires declines and their effector functions are compromised, whereas suppressive factors such as the senescence-associated secretory phenotype (SASP) and myeloid-derived suppressor cells (MDSCs) foster a chronic inflammatory microenvironment conducive to tumor growth. This “aging–inflammation–cancer” axis facilitates tumor immune evasion. Moreover, our present Special Issue aims to examine how immunosenescence influences tumor initiation, progression, metastasis, and therapeutic responses, covering topics from fundamental mechanisms—such as cellular senescence, mitochondrial dysfunction, and epigenetic alterations—to clinical translation, including the challenges of immune checkpoint inhibitors in older patients and the optimization of treatment strategies based on biomarkers of immunosenescence. By highlighting cutting-edge advances in this field, this Special Issue seeks to provide new perspectives on the unique immune landscape of elderly cancer patients and to lay the theoretical groundwork for innovative immunotherapeutic interventions aimed at improving their clinical outcomes.

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