EXTH-141. Immune Rejuvenation via Platelet Factor 4 Alters Tumor Progression in Aged Brain Cancer Models

Abstract Recent studies demonstrate that platelet factor 4 (PF4), an abundant platelet-derived chemokine in young plasma, can reduce neuroinflammation, enhance cognition, and rejuvenate peripheral immunity in aged mice. Intriguingly, neuroimmune markers modulated by PF4—such as Iba1, CD68, and C1q—also contribute to glioma progression. Age-associated immune shifts, including increased myeloid-to-lymphocyte ratios, T cell depletion, and systemic inflammation, are similarly implicated in cancer development. Here, we show that systemic administration of PF4 significantly extends survival in aged (18–23 month-old) glioma-bearing mice and trends toward improved outcomes in young (2–3 month-old) counterparts. Longitudinal IVIS imaging revealed reduced tumor-associated luminescence in PF4-treated animals, particularly in aged males and females. Histological analysis demonstrated downregulation of microglial and macrophage activation markers within the tumor microenvironment. Ongoing studies utilizing flow cytometry, cytokine profiling, and novel PF4-delivery platforms aim to further elucidate its effects on both central and peripheral immunity. These findings suggest that age-related immune modulation may be leveraged to delay glioma progression, positioning PF4 as a promising therapeutic at the intersection of aging, immunology, and neuro-oncology.