Single-cell multiomics reveals macrophage-derived IL-23 and CXCL9/10 drive pathogenic IFNG⁺IL17⁺ T cells in immunotherapy-related colitis.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) therapy, while transformative in cancer treatment, is frequently complicated by immune-related colitis (irColitis), driven by poorly understood mechanisms.

Methods

An integrated analysis of single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR) sequencing, and spatial transcriptomics was conducted to identify immune cell populations and associated signaling pathways driving irColitis. In vivo murine models of irColitis, along with flow cytometry and qPCR, were used to further validate these findings. To assess the functional roles of specific signaling pathways and cell types in driving irColitis, in vivo blockade of IL-23 and CXCL9/10 signaling was performed using neutralizing antibodies, and intestinal macrophages were dep

SUBMITTER: Tang Z 

PROVIDER: S-EPMC12666124 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature