title: Targeting immune checkpoints: New opportunity for mesothelioma treatment?
abstract: Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma.
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: Elly.Marcq@uantwerp.be.
authors.forename: Elly
authors.initials: E
authors.lastname: Marcq
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Pathology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium. Electronic address: Patrick.Pauwels@uza.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Thoracic Oncology/MOCA, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium. Electronic address: Jan.VanMeerbeeck@uza.be.
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.affiliation: Center for Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: Evelien.Smits@uza.be.
authors.forename: Evelien L J
authors.initials: EL
authors.lastname: Smits
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology; D000086002:Mesothelioma, Malignant; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000276:immunology; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000037:antagonists & inhibitors / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007155:Immunologic Factors; D008565:Membrane Proteins; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human
keywords: Cytotoxic T-lymphocyte antigen-4; Immune checkpoint; Immunotherapy; Mesothelioma; Programmed death-1