Molecular predictors of response to pembrolizumab in thymic carcinoma

Thymic carcinoma is rare and has a poorer prognosis than thymomas. The treatment options are limited after failure of platinum-based chemotherapy. We previously performed a single-center phase II study of pembrolizumab in patients with advanced thymic carcinoma, showing a 22.5% response rate. Here, we characterize the genomic and transcriptomic profile of thymic carcinoma samples from 10 patients (5 non-responders versus 5 responders) in this cohort, with the main aim of identifying potential predictors of response to immunotherapy. We find that expression of <i>PDL1</i> and alterations in genes or pathways that correlated with PD-L1 expression (<i>CYLD</i> and <i>BAP1</i>) could be potential predictors for response or resistance to immunotherapy in patients with advanced thymic carcinoma. Our study provides insights into potential predictive markers/pathways to select patients with thymic carcinoma for anti-PD-1 immunotherapy.