Identification of distinct immune signatures in malignant pleural mesothelioma

Radiographic pleural tumor thickness is emerging as an important clinical feature in malignant pleural mesothelioma but the impact of tumor thickness on the complexity of the immune component of the tumor microenvironment is unknown. We are utilizing a multi-omics approach to deeply characterize the tumor immune microenvironment and cellular architecture as it relates to radiographic tumor thickness. Interestingly we have found unique differential gene expression (DE) patterns associated with tumor thickness. Among DE genes (p-value <0.05) we observed enrichment of several MSigDB hallmarks pathways related to immune response and epithelial to mesenchymal transition. Moreover, we observed a unique trend, a decreased expression of immune specific markers in tumors upon increase of radiographic tumor thickness, which was independently confirmed by high order flow cytometry. Additionally, we performed single cell transcriptome profiling of expanded tumor-infiltrating lymphocytes from tumors representing a gradual increase of radiographic tumor thickness, allowing us to track specific immune signatures at the single cell level. Overall, we hope this study will shed light on the complexity of the immune response to MPM, the potential role of radiographic tumor thickness as a biomarker in this setting, and identify actionable targets to improve patient outcome.