Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

“…However, these patient samples were initially studied 10‐20 years ago, and there was not enough tissue left to evaluate the further molecular status between YAP and PD‐L1. Although PD‐1/PD‐L1 inhibitors can be a new treatment option for unresectable MPM with high PD‐L1 expression, the efficacy of PD‐1/PD‐L1 inhibitors is under investigation in clinical trials currently 11, 25, 26. After these clinical trials completed and even anti‐PD‐1/PD‐L1 inhibitors are approved in treating patients with advanced MPM, more patient samples should be gathered to investigate the molecular relevance between YAP and PD‐L1 in the future.…”

Is Pleurectomy/Decortication Superior to Extrapleural Pneumonectomy for Patients with Malignant Pleural Mesothelioma? A Single-Institutional Experience

“…However, the addition of nintedanib to pemetrexed plus cisplatin showed good progression-free survival, 19) as did the use of bevacizumab in the phase-III MAPS trial. 20) Moreover, the use of immune checkpoint inhibitors 21) and multimodal therapy including intraoperative photodynamic therapy 22) has also been reported. Clinical use of these promising treatments is anticipated to improve the survival of patients with MPM.…”

Targeting the epigenome in malignant pleural mesothelioma

“…Collectively, these data support evaluation of DNA demethylating agents in combination with immune checkpoint inhibitors in MPM. Despite evidence that 5-AZA augmented responses to anti-CTLA therapy in preclinical models, a better translational strategy might be to combine DNA demethylating agents with pembrolizumab given recent observations that this PD-L1 inhibitor mediated a 17% objective response rate in MPM patients (134), and high levels of PD-L1 expression in MPM-particularly sarcomatoid subtypes (3). Observations that combined decitabine/GSK126 or 5-AZA/entinostat treatment markedly augment efficacy of adoptively transferred CTL or anti-PD-L1 via up-regulation of Th1 signaling and inhibition of immunosuppressive myeloid derived suppressor cells within the tumor microenvironment in murine cancer models (113,135) support evaluation of such combinatorial regimens in clinical settings.…”