Fig. 7: Anti-TNF therapy improved patients with ICI-induced SJS/TEN and prevented the recurrence of ICI-induced SJS/TEN during re-challenging with ICI therapy with concurrent TNF blockade. | Nature Communications

Fig. 7: Anti-TNF therapy improved patients with ICI-induced SJS/TEN and prevented the recurrence of ICI-induced SJS/TEN during re-challenging with ICI therapy with concurrent TNF blockade.

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

Fig. 7

a 10X Genomic single-cell RNA sequencing (scRNA-seq) analysis in PBMC from three patients with ICI-induced SJS-TEN. UMAP plot generated from a merged dataset of the three patients with ICI-SJS/TEN pre- and post-TNF blockade treatment (total n = 31,904 cells). b UMAP plots segregated according to cellular origin. Dark red indicates the cell clusters before TNF blockade, whereas green indicates those after TNF blockade. Dotted regions highlight cytotoxic cells (including CD8+ T cells and NK/NKT cells) and myeloid/monocyte clusters both before and after TNF blockade. c Pie charts of three ICI-SJS/TEN patients showing relative cluster abundances before and after TNF blockade. The populations of total myeloid/monocyte cells before and after TNF blockade are shown in red. d, e Tumor images in the ICI-induced SJS-TEN overlapping case (ICI-SJS/TEN-1) with metaplastic breast carcinoma were evaluated by computed tomography (CT), revealing a durable complete response after recovery from the SJS/TEN episode. The red arrow indicates the tumor location. f Serial plasma CXCL10, TNF, and GZMB levels in 6 available patients with ICI-induced SJS/TEN during the clinical course from acute to late recovery stages. Day 1 on the horizontal axis is defined as the first day of hospitalization. The arrow in each line chart indicates TNF blockade (etanercept) administration. * of CXCL10 level represent P value calculated by two-sided paired Wilcoxon matched-pairs signed-rank test. g Clinical course, skin presentation, main tumor evaluation by CT, and serial plasma CXCL10 and TNF levels for one patient with ICI-induced SJS/TEN (ICI-SJS/TEN-15) who tolerated to continuous the same type of ICI immunotherapy combined with concurrent TNF blockade. Day 1 on the horizontal axis is defined as the first day of hospitalization. The blue arrow indicates TNF blockade (etanercept) administration time points, and the red arrow indicates the ICI (atezolizumab) treatment and re-challenge time points. The dotted line, arrow range, and values in the CT image indicate the tumor size.

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