Fig. 3: ICI-induced SJS/TEN–related changes in CD8+ T cells and gene expression profiles. | Nature Communications

Fig. 3: ICI-induced SJS/TEN–related changes in CD8+ T cells and gene expression profiles.

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

Fig. 3

a Sub-clustering of CD8+ T cells selected from patients with ICI-induced SJS/TEN, ICI-induced mild cADR, and control participants. A total of 29,134 cells were defined as CD8+ T cells by SingleR annotation and well-studied marker genes. CM: central memory T cells; MAIT: mucosa-associated invariant T cells; Trm: tissue-resident memory T cells. b Violin plots display marker genes for CD8+ T cell clusters. For each cluster, the selected top 10 genes of the highest expression levels with cell type–specificity score, and a highly expressed well-defined subset marker are shown. The y-axis represents the normalized values for gene expression (detailed gene expression profiles for different clusters can be found in Supplementary Fig. 3a). c Frequencies of CD8+ T cells in each cluster for each enrolled patient with ICI-cADR and control participant. ISB: ICI-induced SJS/TEN lesional BC; ISP: ICI-induced SJS/TEN PBMC; IMP: ICI-induced mild cADR (lichenoid dermatitis) PBMC; ITP: ICI-tolerant PBMC; HD: healthy donors PBMC. d Distributions of CD8+ T cells across clusters from ICI-cADR patients and control participants. CD8+ T cell numbers according to group were ISB: 6388 cells; ISP: 4462 cells; IMP: 1570 cells; ITP: 10,319 cells; HD: 6395 cells. e Ranking of the significant and relevant differentially expressed genes (DEG) in CD8+ T cells comparing between ICI-SJS/TEN lesional BC and HD PBMC. f Ranking of the significant and relevant DEG in CD8+ T cells comparing between ICI-SJS/TEN lesional BC and ICI-tolerant (tolerant) PBMC. The significance of DEG was defined a using a two-sided non-parametric Wilcoxon rank-sum test and Bonferroni correction. g The expression patterns of cytotoxic proteins, co-inhibitory receptors, and tumor necrosis factor receptor (TNFR) in UMAP of CD8+ T cell sub-clusters. h Functional enrichment analysis of significant and relevant hallmark gene sets identified as differentially expressed in CD8+ T cells comparing between ICI-SJS/TEN lesional BC and HD PMBC. NES, normalized enrichment score. i Functional enrichment analysis of significant and relevant hallmark gene sets identified as differentially expressed in CD8+ T cells comparing between ICI-SJS/TEN lesional BC and ICI-tolerant (tolerant) PBMC. All significant the significant and relevant differentially expressed genes and hallmark gene sets are shown in the source data.

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