Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab
Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myo...
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2017-12-01
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Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1361097 |
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doaj-a4200e15b90b4e0599622aed5b1577092020-11-25T03:04:25ZengTaylor & Francis GroupOncoImmunology2162-402X2017-12-0161210.1080/2162402X.2017.13610971361097Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumabAlexandre Reuben0Mariana Petaccia de Macedo1Jennifer McQuade2Aron Joon3Zhiyong Ren4Tiffany Calderone5Brandy Conner6Khalida Wani7Zachary A. Cooper8Hussein Tawbi9Michael T. Tetzlaff10Robert F. Padera11Jean-Bernard Durand12Alexander J. Lazar13Jennifer A. Wargo14Michael A. Davies15The University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterBrigham & Women's Hospital, Harvard Medical SchoolThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterThe University of Texas MD Anderson Cancer CenterAutoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis of heart tissue demonstrated findings consistent with giant cell myocarditis (GCM). The immune infiltrate in the heart was largely comprised of CD4+ T cells, whereas the liver had very few T cells, and CD8+ T cells were predominant in the responding lung metastases. TCR sequencing identified high T cell clonality in the lung metastases. The TCR repertoire showed low clonality in the heart and minimal overlap with the liver (1.2%), but some overlap with lung metastases (9.9%). Transcriptional profiling identified several potential mediators of increased inflammation in the heart. These findings provide new insights into the pathogenesis of autoimmune myocarditis with ipilimumab.http://dx.doi.org/10.1080/2162402X.2017.1361097ipilimumabmelanomamyocarditis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandre Reuben Mariana Petaccia de Macedo Jennifer McQuade Aron Joon Zhiyong Ren Tiffany Calderone Brandy Conner Khalida Wani Zachary A. Cooper Hussein Tawbi Michael T. Tetzlaff Robert F. Padera Jean-Bernard Durand Alexander J. Lazar Jennifer A. Wargo Michael A. Davies |
spellingShingle |
Alexandre Reuben Mariana Petaccia de Macedo Jennifer McQuade Aron Joon Zhiyong Ren Tiffany Calderone Brandy Conner Khalida Wani Zachary A. Cooper Hussein Tawbi Michael T. Tetzlaff Robert F. Padera Jean-Bernard Durand Alexander J. Lazar Jennifer A. Wargo Michael A. Davies Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab OncoImmunology ipilimumab melanoma myocarditis |
author_facet |
Alexandre Reuben Mariana Petaccia de Macedo Jennifer McQuade Aron Joon Zhiyong Ren Tiffany Calderone Brandy Conner Khalida Wani Zachary A. Cooper Hussein Tawbi Michael T. Tetzlaff Robert F. Padera Jean-Bernard Durand Alexander J. Lazar Jennifer A. Wargo Michael A. Davies |
author_sort |
Alexandre Reuben |
title |
Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
title_short |
Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
title_full |
Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
title_fullStr |
Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
title_full_unstemmed |
Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
title_sort |
comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2017-12-01 |
description |
Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipilimumab treatment. Histological analysis of heart tissue demonstrated findings consistent with giant cell myocarditis (GCM). The immune infiltrate in the heart was largely comprised of CD4+ T cells, whereas the liver had very few T cells, and CD8+ T cells were predominant in the responding lung metastases. TCR sequencing identified high T cell clonality in the lung metastases. The TCR repertoire showed low clonality in the heart and minimal overlap with the liver (1.2%), but some overlap with lung metastases (9.9%). Transcriptional profiling identified several potential mediators of increased inflammation in the heart. These findings provide new insights into the pathogenesis of autoimmune myocarditis with ipilimumab. |
topic |
ipilimumab melanoma myocarditis |
url |
http://dx.doi.org/10.1080/2162402X.2017.1361097 |
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