Alzheimer's Disease-Associated Amyloid Beta Precursor Protein Prevents Aging Stress-Induced Mitophagy and Fumarate Depletion to Improve Anti-Tumor Immunity.

ABSTRACT: Alzheimer's disease (AD) patients have a decreased incidence of cancer., with a cross-sectional analysis of a nationwide sample of adults finding 21-fold higher odds of cancer diagnosis in non-AD compared to AD patients. Here, we demonstrated that mitochondrial localization of AD-associated amyloid-β precursor protein (APP) and its cleavage product amyloid-β 40, but not mutant APP that lacks a mitochondrial localization signal, inhibits lipid stress-mediated hyperactive mitophagy in aging T-cells, improving their anti-tumor functions. Growth of melanoma xenograft or carcinogen-induced oral cancer models was highly reduced in AD mice. Additionally, adoptive cell transfer (ACT)-based immunotherapy using aging T cells isolated from AD mice suppressed tumor growth. The metabolic signature of s

SUBMITTER: Kassir MF 

PROVIDER: S-EPMC12395851 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature