Abstract
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with limited therapeutic options beyond surgery and cytotoxic chemotherapy. The success of immune checkpoint inhibition has been found to correlate with expression of immune-related genes such as CD274 (PD-L1) in lung and other solid cancers. However, only a small subset of MPM patients respond to checkpoint inhibition, and this response has been varied and unpredictable across several clinical trials. Recent advances in next-generation sequencing (NGS) technology have improved our understanding of the molecular features of MPM, also with respect to its genetic signature and how this impacts the immune microenvironment. This article will review current evidence surrounding the interplay between MPM genetics, including epigenetics and transcriptomics, and the immune response.
Highlights
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor of the pleural cavity
This study suggested that the immunophenotypic variability observed across programmed death ligand 1 (PD-L1) samples may be responsible for the minority of PD-L1–positive mesotheliomas likely to respond to pembrolizumab
As immune checkpoint inhibition gains importance in the treatment of solid tumors including MPM, greater emphasis is being placed on immune characterization and identification of predictive biomarkers for treatment response
Summary
Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program, Division of Thoracic and Cardiovascular Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States. Reviewed by: Fonteneau Jean-Francois, U1232 Centre de Recherche en Cancerologie et Immunologie Nantes Angers (CRCINA) (INSERM), France. Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology. The success of immune checkpoint inhibition has been found to correlate with expression of immune-related genes such as CD274 (PD-L1) in lung and other solid cancers. Only a small subset of MPM patients respond to checkpoint inhibition, and this response has been varied and unpredictable across several clinical trials. This article will review current evidence surrounding the interplay between MPM genetics, including epigenetics and transcriptomics, and the immune response
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