Age-related B cell dysfunction at the aging-cancer nexus: from shared manifestations to therapeutic potential.

Abstract

Aging and cancer are intricately linked through complex, bidirectional interactions, with immune remodeling representing a central point of convergence. Although studies of immune aging have largely centered on T cells, accumulating evidence indicates that B cells also undergo significant functional or phenotypic alterations during aging and tumorigenesis. Here, we introduce the concept of age-related B cell dysfunction to encompass a spectrum of changes that include impaired germinal center response, decline in B cell diversity, expansion of pro-inflammatory phenotypes, and increased autoreactivity. Aging and cancer share fundamental biological hallmarks, including genomic instability, epigenetic reprogramming, chronic inflammation, and dysbiosis, which profoundly reshape immune cell states. In this review, we synthesize emerging mechanistic evidence linking these processes to maladaptive B cell programs across tissues and tumor contexts, and discuss how such alterations influence tumor evolution, responses to therapy, and treatment-related toxicities. Finally, we highlight emerging strategies targeting age-related dysfunctional B cells in cancer, illustrating how insights from biology of aging and tumor immunology could inform future translational approaches.