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JCI Insight. 2018 Apr 5;3(7). pii: 98575. doi: 10.1172/jci.insight.98575. eCollection 2018 Apr 5.

Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

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Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery.
Department of Biochemistry and Molecular Biology.
Section of Hematology-Oncology, Department of Medicine.
Department of Radiology, and.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Division of Abdominal Transplantation, Immune Evaluation Laboratory, Michael E. DeBakey Department of Surgery, and.
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, Texas, USA.


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.


Cancer immunotherapy; Expression profiling; Immunology; Oncology; Proteomics

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