Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy
2026-07-21
Chronic inflammation increases with age and contributes to cancer progression and therapeutic resistance, yet the mechanisms underlying this process remain incompletely understood. Here, we identify an increased frequency of pro-inflammatory myeloid cells in aged mice and humans, characterized by elevated production of IL-1α, IL-1β, IL-6, and TNF-α. These cells are enriched in the breast tumor microenvironment and are associated with accelerated tumor progression. Using heterochronic parabiosis and bone marrow chimeras, we show that age-associated myeloid cell inflammatory activation is suppressed by non-bone marrow-derived circulating factors present in young hosts. Integrative analyses identify thymulin, a thymus-derived peptide that declines with age, as a mediator that suppresses pro-inflammatory cytokine production by inhibiting NF-κB signaling. Furthermore, thymulin enhances antitumor T-cell immunity, improves tumor control and survival, and sensitizes tumors to anti-PD-L1 therapy in an age-dependent manner. Together, these findings uncover a thymus–myeloid cell regulatory axis linking aging, inflammation, and cancer immunity, and suggest thymulin as a potential strategy to improve cancer immunotherapy in older individuals.