Tumor-associated neutrophils suppress CD8⁺ T cell immunity in urothelial bladder carcinoma through the COX-2/PGE2/IDO1 Axis.

ABSTRACT:

Background

Many urothelial bladder carcinoma (UBC) patients don't respond to immune checkpoint blockade (ICB) therapy, possibly due to tumor-associated neutrophils (TANs) suppressing lymphocyte immune response.

Methods

We conducted a meta-analysis on the predictive value of neutrophil-lymphocyte ratio (NLR) in ICB response and investigated TANs' role in UBC. We used RNA-sequencing, HALO spatial analysis, single-cell RNA-sequencing, and flow cytometry to study the impacts of TANs and prostaglandin E2 (PGE2) on IDO1 expression. Animal experiments evaluated celecoxib's efficacy in targeting PGE2 synthesis.

Results

Our analysis showed that higher TAN infiltration predicted worse outcomes in UBC patients receiving ICB therapy. Our research revealed that TANs promote IDO1 e

SUBMITTER: Ouyang Y 

PROVIDER: S-EPMC10912642 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature