The impact of aging on antitumor immunity and cancer immunotherapy

Aging is the first risk factor associated with cancer, predominantly due to cumulative somatic mutations and a profound decline in antitumor immunity. The aging process remodels immune function across hematopoietic, adaptive, and innate compartments through interconnected processes, including hematopoietic stem cell dysfunction, loss of metabolic fitness, altered B and T cell phenotypes, myeloid skewing, and a complex interplay between cellular senescence and inflammaging. These changes collectively establish an immunosuppressive landscape that weakens natural tumor surveillance and constrains responses to cancer immunotherapies. Given the shift toward an aging global population and the disproportionate cancer burden in older individuals, we emphasize the clinical relevance of patient-stratification strategies. We further discuss emerging approaches aimed at rejuvenating immune function to improve immunotherapy outcomes in older patients.