Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments antitumor activity in melanoma.

ABSTRACT: Targeting tumor-associated blood vessels to increase immune infiltration may enhance treatment effectiveness, yet limited data exist regarding anti-angiogenesis effects on the tumor microenvironment (TME). We hypothesized that dual targeting of angiogenesis with immune checkpoints would improve both intracranial and extracranial disease. We used subcutaneous and left ventricle melanoma models to evaluate anti-PD-1/anti-VEGF and anti-PD-1/lenvatinib (pan-VEGFR inhibitor) combinations. Cytokine/chemokine profiling and flow cytometry were performed to assess signaling and immune-infiltrating populations. An in vitro blood-brain barrier (BBB) model was utilized to study intracranial treatment effects on endothelial integrity and leukocyte transmigration. Anti-PD-1 with either anti-VEGF or lenv

SUBMITTER: Tran TT 

PROVIDER: S-EPMC10132152 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature