Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis
Objective This study aimed to explore the shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis (ICIM) and autoimmune myocarditis. Methods Relevant data were retrieved from public datasets and Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GS...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-12-01
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| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/1721727X231223578 |
| _version_ | 1797356491837014016 |
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| author | Kai Yang Min Zhang Dong Li Yuandong Yu Fengjun Cao Guoxing Wan |
| author_facet | Kai Yang Min Zhang Dong Li Yuandong Yu Fengjun Cao Guoxing Wan |
| author_sort | Kai Yang |
| collection | DOAJ |
| description | Objective This study aimed to explore the shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis (ICIM) and autoimmune myocarditis. Methods Relevant data were retrieved from public datasets and Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) of differentially expressed genes (DEGs) was used to identify significant shared signaling pathways between ICIM and non-ICI associated autoimmune myocarditis (NICIAM) represented by ICIM model and experimental autoimmune myocarditis (EAM) model, respectively. Cell type enrichment analysis and immune infiltration analysis by clusterProfiler and ImmuCellAI were performed to identify critical immune cell component involved in ICIM and NICIAM. Additionally, core shared genes across ICIM and NICIAM were identified and validated by various models and methods. Results Interferon-γ response, inflammatory response and allograft rejection signaling were identified as the shared signaling pathways associated with ICIM and NICIAM. Enrichment analysis of cell type supported an important role of increased infiltration of T cells and macrophages in both ICIM and NICIAM. However, the predominant increase of infiltrated T cells was CD4+ T cells in NICIAM, while that were CD8+ T cells in ICIM. Core shared genes Lck and Cd3d expression were found increased in both ICIM and NICIAM, and Lck inhibition was further identified and validated as potential therapeutic approach. Conclusions Our study initially established a comorbidity model to identify potential molecular mechanism including interferon-γ response, inflammatory response and allograft rejection signaling accounting for the concerns of myocarditis risk in patients with preexisting autoimmune disease (PAD) receiving ICI treatment, and supported the therapeutic potential of targeting Lck or Cd3d. |
| first_indexed | 2024-03-08T14:27:27Z |
| format | Article |
| id | doaj.art-bf9e0e9a31de4cba862addcf26629a34 |
| institution | Directory Open Access Journal |
| issn | 2058-7392 |
| language | English |
| last_indexed | 2024-03-08T14:27:27Z |
| publishDate | 2024-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-bf9e0e9a31de4cba862addcf26629a342024-01-12T22:04:00ZengSAGE PublishingEuropean Journal of Inflammation2058-73922024-12-012210.1177/1721727X231223578Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditisKai YangMin ZhangDong LiYuandong YuFengjun CaoGuoxing WanObjective This study aimed to explore the shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis (ICIM) and autoimmune myocarditis. Methods Relevant data were retrieved from public datasets and Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) of differentially expressed genes (DEGs) was used to identify significant shared signaling pathways between ICIM and non-ICI associated autoimmune myocarditis (NICIAM) represented by ICIM model and experimental autoimmune myocarditis (EAM) model, respectively. Cell type enrichment analysis and immune infiltration analysis by clusterProfiler and ImmuCellAI were performed to identify critical immune cell component involved in ICIM and NICIAM. Additionally, core shared genes across ICIM and NICIAM were identified and validated by various models and methods. Results Interferon-γ response, inflammatory response and allograft rejection signaling were identified as the shared signaling pathways associated with ICIM and NICIAM. Enrichment analysis of cell type supported an important role of increased infiltration of T cells and macrophages in both ICIM and NICIAM. However, the predominant increase of infiltrated T cells was CD4+ T cells in NICIAM, while that were CD8+ T cells in ICIM. Core shared genes Lck and Cd3d expression were found increased in both ICIM and NICIAM, and Lck inhibition was further identified and validated as potential therapeutic approach. Conclusions Our study initially established a comorbidity model to identify potential molecular mechanism including interferon-γ response, inflammatory response and allograft rejection signaling accounting for the concerns of myocarditis risk in patients with preexisting autoimmune disease (PAD) receiving ICI treatment, and supported the therapeutic potential of targeting Lck or Cd3d.https://doi.org/10.1177/1721727X231223578 |
| spellingShingle | Kai Yang Min Zhang Dong Li Yuandong Yu Fengjun Cao Guoxing Wan Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis European Journal of Inflammation |
| title | Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis |
| title_full | Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis |
| title_fullStr | Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis |
| title_full_unstemmed | Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis |
| title_short | Identification of shared mechanisms and targets between immune checkpoint inhibitor-associated myocarditis and autoimmune myocarditis |
| title_sort | identification of shared mechanisms and targets between immune checkpoint inhibitor associated myocarditis and autoimmune myocarditis |
| url | https://doi.org/10.1177/1721727X231223578 |
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