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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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Detalles Bibliográficos
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
Descripción
Sumario: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.