High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway.

ABSTRACT:

Background

Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor (ICI) treatment. This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high (HTB) and low (LTB) tumor burden.

Methods

For in vivo studies, several mouse models of subcutaneous tumors were established, and transcriptome sequencing, immunohistochemistry, and flow cytometry assays were used to detect the immune status in these subcutaneous tumors. For in vitro experiments, co-culture models, cytokine antibody arrays, western blotting, flow cytometry, and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms RESULTS:

SUBMITTER: Wen Z 

PROVIDER: S-EPMC10174084 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature