Tumor-derived lactate inhibit the efficacy of lenvatinib through regulating PD-L1 expression on neutrophil in hepatocellular carcinoma.

ABSTRACT:

Background

Neutrophils play a controversial role in tumor development. The function of programmed cell death-1 ligand (PD-L1⁺) neutrophils, however, may inhibit the cytotoxicity of anti-tumor immunity. In this study, we elucidate the stimulators of PD-L1⁺ neutrophils in tumor microenvironment (TME) and explore the optimal combination to enhance the effect of lenvatinib by inhibiting PD-L1⁺ neutrophils in hepatocellular carcinoma.

Methods

Neutrophil infiltration after lenvatinib treatment was examined with RNA sequencing and multicolor flow cytometry analysis in patient samples, subcutaneous and orthotopic mouse models. Neutrophils and T cells were isolated from peripheral blood and tumor tissues and purified with magnetic beads for cytotoxici

SUBMITTER: Deng H 

PROVIDER: S-EPMC8231064 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature