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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

General Review Article

Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma

Author(s): Lei Cheng, Na Li, Xiao-ling Xu* and Wei-Min Mao*

Volume 21 , Issue 15 , 2020

Page: [1606 - 1612] Pages: 7

DOI: 10.2174/1389450121666200719011234

Price: $65

Abstract

Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.

Keywords: Malignant Pleural Mesothelioma (MPM), Tumor Immune Microenvironment (TME), heterogeneity, immunotherapy, molecular pathways, Non-Small-Cell Lung Cancer (NSCLC).

Graphical Abstract
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