Fig. 4: The connectivity between CD8⁺ T cells and macrophage/monocyte/myeloid cells in patients with ICI-induced SJS/TEN and mild cADR.

a Analysis of chemokine receptor–ligand pairs (CXCR3–CXCL9 and CXCR3–CXCL10) across clusters in all cell datasets shown in Fig. 1d. The “ICI-SJS/TEN” group includes lesional BC and PBMC from 5 patients with ICI-induced SJS/TEN patients, and the “ICI-tolerant & HD” group includes PBMC from 5 ICI-tolerant patients and 6 healthy donors (HD). b The scaled and normalized gene expression levels for CXCL9 and CXCL10 in all cell datasets (related to Fig. 1d) was shown, whereas the violin plot and heatmap beneath was drawn from the subset of macrophage/monocyte/myeloid clusters. c The scaled and normalized expression levels of CXCR3 in all cell datasets (related to Fig. 1d) were shown, whereas the violin plot and heatmap beneath were drawn from the subset of CD8⁺ T cell clusters. ISB: ICI-SJS/TEN lesional BC; ISP: ICI-SJS/TEN PBMC; IMP: ICI-mild cADR PBMC; ITP: ICI-tolerant PBMC; HD: healthy donors PBMC. d Heatmap showing Z score–normalized averaged expression levels of the indicated cytokines/cytotoxic proteins/inflammatory proteins and its related receptor genes compared among ICI-SJS/TEN, ICI-mild cADR, and control groups. The normalized differential gene expression (DEG) levels in CD8⁺ T cell clusters (clusters 3–7 in Fig. 1d; defined by SingleR annotation) and macrophage/monocyte/myeloid clusters (clusters 9–14 in Fig. 1d; defined by SingleR annotation) were shown. The indicated relevant genes list is based on the significant P values for ICI-SJS/TEN lesional BC group comparing to “ICI-tolerant & HD” group, which were calculated by Wilcoxon rank-sum test. The genes associated with the TNF signaling pathway were denoted in a red color. e Scatterplot showing DEG, confirming RNA expression levels in formalin-fixed paraffin-embedded (FFPE) skin tissue samples from patients with ICI-induced SJS–TEN (ICI-SJS/TEN; n = 5) or ICI-induced lichenoid dermatitis (ICI-mild cADR; n = 7) compared with those from HD (HD; n = 8). Each dot denotes an individual gene with a Benjamini–Hochberg-adjusted P value (two-sided unpaired Mann–Whitney U test) <0.05 and average log₂ fold change (FC) > 2 in ICI-SJS/TEN samples compared with HD samples (ICI-SJS/TEN vs. HD) and in ICI-mild cADR samples compared with HD samples (ICI-mild cADR vs. HD). The blue-labeled genes represent genes that were significantly elevated in both the ICI-SJS/TEN vs. HD and ICI-mild cADR vs. HD comparisons, whereas the red-labeled genes were only significantly elevated in the ICI-SJS/TEN vs. HD comparison. f Immunofluorescence staining with anti-CD8 (green) and anti-CXCR3 (red) antibodies, and 4’,6-diamidino-2-phenylindole (DAPI; nuclear stain; blue) in skin tissues from 7 patients with ICI-SJS/TEN and 4 ICI-mild cADR and from 4 HD control participants (sample list shown in source data). The upper figures represent 200×, whereas the lower figures represent 400× magnification. g Immunofluorescence staining with anti-CXCL10 (green) and anti-CD163 (red) antibodies and DAPI (blue). The upper figures represent 200×, whereas the lower figures represent 400× magnification.