Fig. 9. cGAS-STING signalling mediates aPD-1 therapy-induced myocarditis.

A A schematic graph showing the procedure of isobaric Tandem Mass Tagging (TMT)-based multiplexed quantitative proteomic analysis in heart of WT and Gsdme^−/− mice received aPD-1 therapy. B Volcano plot showing the upregulated and downregulated proteins identified by TMT quantitative proteomic analysis. C Heatmaps showing the top 20 up-regulated and down-regulated proteins in Gsdme^−/− mice heart compared with WT mice heart upon aPD-1 therapy. D The potential protein-protein interaction among the top differentially regulated proteins between WT and Gsdme^−/− mice heart upon aPD-1 therapy. The protein-protein interaction network analysis was performed with STRING database v 11.0. E Top enriched pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) database with the most differentially regulated proteins between WT and Gsdme^−/− mice heart upon aPD-1 therapy. F Top enriched pathways in Gene Ontology (GO) knowledgebase with the most differentially regulated proteins between WT and Gsdme^−/− mice heart upon aPD-1 therapy. G, H The plasma levels of mtDNA and double stranded DNA (dsDNA) in WT and Gsdme^−/− mice heart upon aPD-1 therapy. I Expression of cGAS, STING, phospho-TBK1 (p-TBK1), total-TBK1, phospho-IRF3 (p-IRF3) and total-IRF3 in heart of WT and Gsdme^−/− mice received aPD-1 therapy or control IgG were determined using immunoblotting. J Representative echocardiograms and quantitative analysis of cardiac function in WT and Sting^gt/gt mice received aPD-1 therapy. K Serum cTnT and cTnI concentrations of WT and Sting^gt/gt mice received aPD-1 therapy or control IgG. L Cleavage of GSDME in WT and Sting^gt/gt mice received aPD-1 therapy or control IgG. M Representative flow cytometry showing the proportions of CD4⁺ and CD8⁺ cells in heart of WT and Sting^gt/gt mice received aPD-1 therapy. The data were presented as means ± SEM and analyzed by two-sided unpaired Student’s t-tests. n = 6 biologically independent experiments.