Copper chelation redirects neutrophil function to enhance anti-GD2 antibody therapy in neuroblastoma.

ABSTRACT: Anti-disialoganglioside (GD2) antibody therapy has provided clinical benefit to patients with neuroblastoma however efficacy is likely impaired by the immunosuppressive tumor microenvironment. We have previously defined a link between intratumoral copper levels and immune evasion. Here, we report that adjuvant copper chelation potentiates anti-GD2 antibody therapy to confer durable tumor control in immunocompetent models of neuroblastoma. Mechanistic studies reveal copper chelation creates an immune-primed tumor microenvironment through enhanced infiltration and activity of Fc-receptor-bearing cells, specifically neutrophils which are emerging as key effectors of antibody therapy. Moreover, we report copper sequestration by neuroblastoma attenuates neutrophil function which can be successf

SUBMITTER: Rouaen JRC 

PROVIDER: S-EPMC11638255 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature