Integrated analysis of somatic mutations and immune microenvironment in malignant pleural mesothelioma Journal Article

Authors: Kiyotani, K.; Park, J. H.; Inoue, H.; Husain, A.; Olugbile, S.; Zewde, M.; Nakamura, Y; Vigneswaran, W. T.
Article Title: Integrated analysis of somatic mutations and immune microenvironment in malignant pleural mesothelioma
Abstract: To investigate the link between the genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity of somatic mutations of cancer cells and TILs (T-cell receptor beta (TCRbeta) repertoire), and expression profiles of immune-related genes using specimens of three different tumor sites (anterior, posterior, and diaphragm) obtained from six MPM patients. Integrated analysis identified the distinct patterns of somatic mutations and the immune microenvironment signatures both intratumorally and interindividually. MPM cases showed intratumoral heterogeneity in somatic mutations with unique TCRbeta clonotypes of TILs that were restricted to each tumor site, suggesting the presence of a neoantigen-related immune response. Correlation analyses showed that higher neoantigen load was significantly correlated with stronger clonal expansion of TILs (p = 0.048) and a higher expression level of an immune-associated cytolytic factor (PRF1 (p = 0.0041) in tumor tissues), suggesting that high neoantigen loads in tumor cells might promote expansion of functional tumor-specific T cells in the tumor bed. Our results collectively indicate that MPM tumors constitute a diverse heterogeneity in both the genomic landscape and immune microenvironment, and that mutation/neoantigen load may affect the immune microenvironment in MPM tissues.
Journal Title: Oncoimmunology
Volume: 6
Issue: 2
ISSN: 2162-4011; 2162-4011
Publisher: Unknown  
Journal Place: United States
Date Published: 2017
Start Page: e1278330
Language: eng
Notes: LR: 20170403; JID: 101570526; OTO: NOTNLM; PMCR: 2018/01/06; 2016/11/17 [received]; 2016/12/27 [revised]; 2016/12/28 [accepted]; epublish