In Silico Immune Response is the Most Predictive Factor of Overall Survival in Surgically Resected Pleural Mesothelioma
Objective: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that is fatal. Recent evidence has suggested that MPM is an immunogenic tumor that responds favorably to immunotherapy including checkpoint inhibition. We set out to dissect the immune landscape of MPM using mRNA transcriptome data to identify novel immune biomarkers of prognosis and to potentially predict response to immunotherapy.
Methods: Immune Response In Silico (IRIS) is a collection of genes selected based upon their specific expression in immune cells. We analyzed the IRIS gene profile from mRNA expression data of 158 tumors from patients undergoing surgical resection of MPM. A discovery set was comprised of mRNA sequencing data from tumors of 69 patients in TCGA database. OS-associated IRIS (OSIRIS) signatures were validated in two independent cohorts obtained from MPM treatment centers in the United States (n=39 and n=50).
Conclusions: The novel OSIRIS prediction model constructed with immune-related genes can predict survival independently, and superior to TNM staging and histology in patients with MPM. This signature holds promise for prediction of response to immunotherapy in this disease and will be tested in a single institution clinical trial of checkpoint inhibition in MPM.