Integrated analysis of somatic genetic alterations and immune microenvironment in malignant pleural mesothelioma.

e20080Background: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor and rapidly fatal when untreated. Advanced high-throughput sequencing technologies allow comprehensive characterization of genetic alterations in tumors. Genomic landscape of MPM is not well understood. Knowledge of immune microenvironment of MPM is critical for developing effective targeted therapies. Methods: We examined biopsies from 12 MPM patients that were removed during maximal cyto-reductive surgery. Specimens from 3 sites (anterior, posterior and diaphragm, a total of 36 tissue samples) were studied through whole exome sequencing, T cell receptor (TCR) repertoire analysis of tumor-infiltrating T cells (TILs), and expression levels of immune-related genes. We also performed in silicoprediction of potent neoantigens derived from non-synonymous somatic mutations in each specimen. Tumor tissues from 3 sites were compared using hierarchical clustering for tumor heterogeneity and differences in immune environment. Result...