A novel polyamine blockade therapy activates an anti-tumor immune response.

ABSTRACT: Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4⁺ and CD8⁺ T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent. The PBT anti-tumor effect was accompanied by an increase in granzyme B⁺, IFN-γ⁺ CD8<

SUBMITTER: Alexander ET 

PROVIDER: S-EPMC5663583 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature