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Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma

We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition,...

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Autores principales: Lee, Hyun-Sung, Jang, Hee-Jin, Choi, Jong Min, Zhang, Jun, de Rosen, Veronica Lenge, Wheeler, Thomas M., Lee, Ju-Seog, Tu, Thuydung, Jindra, Peter T., Kerman, Ronald H., Jung, Sung Yun, Kheradmand, Farrah, Sugarbaker, David J., Burt, Bryan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928857/
https://www.ncbi.nlm.nih.gov/pubmed/29618661
http://dx.doi.org/10.1172/jci.insight.98575
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author Lee, Hyun-Sung
Jang, Hee-Jin
Choi, Jong Min
Zhang, Jun
de Rosen, Veronica Lenge
Wheeler, Thomas M.
Lee, Ju-Seog
Tu, Thuydung
Jindra, Peter T.
Kerman, Ronald H.
Jung, Sung Yun
Kheradmand, Farrah
Sugarbaker, David J.
Burt, Bryan M.
author_facet Lee, Hyun-Sung
Jang, Hee-Jin
Choi, Jong Min
Zhang, Jun
de Rosen, Veronica Lenge
Wheeler, Thomas M.
Lee, Ju-Seog
Tu, Thuydung
Jindra, Peter T.
Kerman, Ronald H.
Jung, Sung Yun
Kheradmand, Farrah
Sugarbaker, David J.
Burt, Bryan M.
author_sort Lee, Hyun-Sung
collection PubMed
description We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes. This molecular signature, representative of a favorable intratumoral cell network, was independently associated with improved survival in MPM and predicted response to immune checkpoint inhibitors in patients with MPM and melanoma. These data additionally suggest a potentially novel mechanism of response to checkpoint blockade: requirement for high measured abundance of neopeptides in the presence of high expression of MHC proteins specific for these neopeptides.
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spelling pubmed-59288572018-05-03 Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma Lee, Hyun-Sung Jang, Hee-Jin Choi, Jong Min Zhang, Jun de Rosen, Veronica Lenge Wheeler, Thomas M. Lee, Ju-Seog Tu, Thuydung Jindra, Peter T. Kerman, Ronald H. Jung, Sung Yun Kheradmand, Farrah Sugarbaker, David J. Burt, Bryan M. JCI Insight Research Article We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes. This molecular signature, representative of a favorable intratumoral cell network, was independently associated with improved survival in MPM and predicted response to immune checkpoint inhibitors in patients with MPM and melanoma. These data additionally suggest a potentially novel mechanism of response to checkpoint blockade: requirement for high measured abundance of neopeptides in the presence of high expression of MHC proteins specific for these neopeptides. American Society for Clinical Investigation 2018-04-05 /pmc/articles/PMC5928857/ /pubmed/29618661 http://dx.doi.org/10.1172/jci.insight.98575 Text en Copyright © 2018 Lee et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Lee, Hyun-Sung
Jang, Hee-Jin
Choi, Jong Min
Zhang, Jun
de Rosen, Veronica Lenge
Wheeler, Thomas M.
Lee, Ju-Seog
Tu, Thuydung
Jindra, Peter T.
Kerman, Ronald H.
Jung, Sung Yun
Kheradmand, Farrah
Sugarbaker, David J.
Burt, Bryan M.
Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title_full Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title_fullStr Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title_full_unstemmed Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title_short Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
title_sort comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928857/
https://www.ncbi.nlm.nih.gov/pubmed/29618661
http://dx.doi.org/10.1172/jci.insight.98575
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