Immunotherapeutic Approaches in Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.

Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy

“…6 7 The broader immunotherapeutic landscape of MPM has been comprehensively reviewed recently. [8][9][10][11][12] The intimate involvement and abundance of leukocytes in MPM 13 from carcinogenesis to diagnosis suggest that the tumor immune microenvironment's (TIME's) composition may influence response to immunotherapy 14 and the tumor's genomic landscape. 15 This review article will focus on cytotoxic T-lymphocyte (CTL) biology and the specific role of TAMs in immunosuppression.…”

Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27Kip1

“…The survival rate for patients with malignant pleural mesothelioma is still low; a population-based study reported average survival times ranging from 5 months to 13.2 months ( 25 ). Although immunotherapeutic approaches to malignant mesothelioma have received much attention, further studies are needed to show a clear advantage over standard chemotherapy ( 26 ). A recent study of immunotherapeutic approach also showed significant and clinically meaningful improvements in overall survival versus standard chemotherapy ( 27 ).…”

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma

“…A better treatment is urgently needed. Biological targeted therapy for MPM is not recommended because of the lack of known oncogenic driver alterations (7). Clinical studies of MPM immunotherapy has underwent a transition from relapse to second-line, monotherapy to combination, and now seemed promising in some phase II clinical studies (8).…”