Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

Autor:	Lee HS; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery., Jang HJ; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery., Choi JM; Department of Biochemistry and Molecular Biology., Zhang J; Section of Hematology-Oncology, Department of Medicine., de Rosen VL; Department of Radiology, and., Wheeler TM; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA., Lee JS; Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Tu T; Division of Abdominal Transplantation, Immune Evaluation Laboratory, Michael E. DeBakey Department of Surgery, and., Jindra PT; Division of Abdominal Transplantation, Immune Evaluation Laboratory, Michael E. DeBakey Department of Surgery, and., Kerman RH; Division of Abdominal Transplantation, Immune Evaluation Laboratory, Michael E. DeBakey Department of Surgery, and., Jung SY; Department of Biochemistry and Molecular Biology., Kheradmand F; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.; Department of Medicine, Baylor College of Medicine, Houston, Texas, USA., Sugarbaker DJ; Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, Texas, USA., Burt BM; Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2018 Apr 05; Vol. 3 (7). Date of Electronic Publication: 2018 Apr 05 (Print Publication: 2018).
DOI:	10.1172/jci.insight.98575
Abstrakt:	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.
Databáze:	MEDLINE
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