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Role of regorafenib in macrophage and in antitumor immunity in hepatocellular carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE148950 | GEO | 2021/01/27

REPOSITORIES: GEO

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Role of regorafenib in antitumor immunity in hepatocellular carcinoma

Project description:Low-dose regorafenib (5 mg/kg/day, corresponding to about half of human clinical dosage) inhibited tumor growth and angiogenesis in vivo similarly to DC-101 (anti-VEGFR antibody) but produced higher T cell activation and M1 macrophage polarization, Regorafenib increased M1/M2 ratio of BMDMs polarization and proliferation/activation of co-cultured T cells in vitro, indicating angiogenesis-independent immunomodulatory effects. Suppression of p38 kinase phosphorylation and downstream CREB-KLF4 activity in BMDMs by regorafenib reversed M2 polarization. Regorafenib enhanced antitumor efficacy of adoptively transferred antigen-specific T cells, whereas macrophage deletion negated regorafenib’s antitumor effects. Synergistic antitumor efficacy between low-dose regorafenib and anti-PD1 was associated with multiple immune-related pathways in the tumor microenvironment.

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