Title:Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma
Volume: 21
Issue: 15
Author(s): Lei Cheng, Na Li, Xiao-ling Xu*Wei-Min Mao*
Affiliation:
- Department of Thoracic Surgery Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang,China
- Department of Thoracic Surgery Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang,China
Keywords:
Malignant Pleural Mesothelioma (MPM), Tumor Immune Microenvironment (TME), heterogeneity, immunotherapy,
molecular pathways, Non-Small-Cell Lung Cancer (NSCLC).
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.
