Abstract
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.
Original language | English (US) |
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Journal | JCI Insight |
Volume | 3 |
Issue number | 7 |
DOIs | |
State | Published - Apr 5 2018 |
Keywords
- Cancer immunotherapy
- Expression profiling
- Immunology
- Oncology
- Proteomics
ASJC Scopus subject areas
- General Medicine
MD Anderson CCSG core facilities
- Flow Cytometry and Cellular Imaging Facility