Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

ABSTRACT: Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3⁺ cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions. ScRNA expression profiles and ex vivo blocking studies further identify TNF signaling as a pathway responsible for macrophage-derived CXCL10 and CTL activation. Based on the trajectory analysis, ICI-activated T ce

SUBMITTER: Chen CB 

PROVIDER: S-EPMC11685864 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature