Thymic regeneration and tumor immunotherapy

The thymus, as a vital immune organ in the human body, provides the essential microenvironment for the development, differentiation, and maturation of T lymphocytes. With advancing age, the thymus gradually undergoes atrophy and degeneration, primarily characterized by structural disruption of thymic epithelial cells, leading to slowed T cell development and reduced output. Experimental studies have identified multiple regenerative pathways, including IL-7, KGF, BMP4, IL-22, RANKL, regulatory T cells, FOXN1-directed approaches, and sex-steroid blockade. Recent human observational studies also associate preserved thymic health with lower disease risk and better outcomes after cancer immunotherapy. However, most regenerative interventions remain preclinical, and no thymus-directed strategy has yet been shown to improve cancer immunotherapy outcomes in a randomized clinical trial. This review summarizes mechanisms of thymic involution and injury, evaluates regenerative strategies according to evidence level, and discusses the opportunities, limitations, and safety considerations for translating thymic regeneration into cancer care.