Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease
Abstract Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological...
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2021
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oai:doaj.org-article:343f8400bbfa4428b6c1537bc05410f12021-12-02T16:56:10ZClinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease10.1038/s41598-021-88824-12045-2322https://doaj.org/article/343f8400bbfa4428b6c1537bc05410f12021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88824-1https://doaj.org/toc/2045-2322Abstract Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.Satoru HagiwaraTomohiro WatanabeMasatoshi KudoKosuke MinagaYoriaki KomedaKen KamataMasatomo KimuraHidetoshi HayashiKazuhiko NakagawaKazuomi UeshimaYasunori MinamiTomoko AokiMasahiro TakitaMasahiro MoritaHirokazu CishinaHiroshi IdaAh-Mee ParkNaoshi NishidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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DOAJ |
| collection |
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| topic |
Medicine R Science Q |
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Medicine R Science Q Satoru Hagiwara Tomohiro Watanabe Masatoshi Kudo Kosuke Minaga Yoriaki Komeda Ken Kamata Masatomo Kimura Hidetoshi Hayashi Kazuhiko Nakagawa Kazuomi Ueshima Yasunori Minami Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Cishina Hiroshi Ida Ah-Mee Park Naoshi Nishida Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| description |
Abstract Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs. |
| format |
article |
| author |
Satoru Hagiwara Tomohiro Watanabe Masatoshi Kudo Kosuke Minaga Yoriaki Komeda Ken Kamata Masatomo Kimura Hidetoshi Hayashi Kazuhiko Nakagawa Kazuomi Ueshima Yasunori Minami Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Cishina Hiroshi Ida Ah-Mee Park Naoshi Nishida |
| author_facet |
Satoru Hagiwara Tomohiro Watanabe Masatoshi Kudo Kosuke Minaga Yoriaki Komeda Ken Kamata Masatomo Kimura Hidetoshi Hayashi Kazuhiko Nakagawa Kazuomi Ueshima Yasunori Minami Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Cishina Hiroshi Ida Ah-Mee Park Naoshi Nishida |
| author_sort |
Satoru Hagiwara |
| title |
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| title_short |
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| title_full |
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| title_fullStr |
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| title_full_unstemmed |
Clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| title_sort |
clinicopathological analysis of hepatic immune-related adverse events in comparison with autoimmune hepatitis and graft-versus host disease |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/343f8400bbfa4428b6c1537bc05410f1 |
| work_keys_str_mv |
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| _version_ |
1718382792565325824 |