Common germline variants of the human APOE gene modulate melanoma progression and survival.

ABSTRACT: Common germline variants of the APOE gene are major risk modifiers of neurodegenerative and atherosclerotic diseases^1-3, but their effect on cancer outcome is poorly defined. Here we report that, in a reversal of their effect on Alzheimer's disease, the APOE4 and APOE2 variants confer favorable and poor outcomes in melanoma, respectively. Mice expressing the human APOE4 allele exhibited reduced melanoma progression and metastasis relative to APOE2 mice. APOE4 mice exhibited enhanced anti-tumor immune activation relative to APOE2 mice, and T cell depletion experiments showed that the effect of APOE genotype on melanoma progression was mediated by altered anti-tumor immunity. Consistently, patients with melanoma carrying the APOE4 variant experienced improved survival in compariso

SUBMITTER: Ostendorf BN 

PROVIDER: S-EPMC8058866 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature