Conquering aging-related immunosenescence and tumor immune escape

With global population aging, senescence has emerged as a key driver of tumorigenesis. Aging-associated molecular changes, including DNA damage, telomere shortening, and epigenetic dysregulation, increase malignancy, while immunosenescence and the senescence-associated secretory phenotype (SASP), reshape the tumor microenvironment to favor immune suppression and tumor escape. Aging also impairs antigen presentation, disrupts ligand-receptor signaling, and compromises tumor suppressive pathways. In the era of immunotherapy, elderly patients face reduced efficacy and increased resistance due to age-related immune remodeling. This review summarizes mechanisms of tumor immune escape in aging and discusses strategies to improve outcomes, such as senescent cell clearance, SASP modulation, immune potentiation, and combination therapies.