{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:57:49Z","timestamp":1791734269533,"version":"4.3.4"},"reference-count":155,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.<\/jats:p>","DOI":"10.3390\/cancers13225664","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T08:10:22Z","timestamp":1636704622000},"page":"5664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms"],"prefix":"10.3390","volume":"13","author":[{"given":"Francesca","family":"Cersosimo","sequence":"first","affiliation":[{"name":"Department of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-9814","authenticated-orcid":false,"given":"Marcella","family":"Barbarino","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0307-4163","authenticated-orcid":false,"given":"Silvia","family":"Lonardi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2291-2997","authenticated-orcid":false,"given":"William","family":"Vermi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, Italy"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-016X","authenticated-orcid":false,"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6119-9007","authenticated-orcid":false,"given":"Cristiana","family":"Bellan","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-6449","authenticated-orcid":false,"given":"Emanuele","family":"Giurisato","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"},{"name":"Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16766","DOI":"10.18632\/oncotarget.4414","article-title":"Distinctive clinical characteristics of malignant mesothelioma in young patients","volume":"6","author":"Thomas","year":"2015","journal-title":"Oncotarget"},{"key":"ref_2","unstructured":"FDA: U.S. Food and Drug Administration (2021, September 26). FDA Approves Drug Combination For Treating Mesothelioma, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-drug-combination-treating-mesothelioma."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrc.2017.42","article-title":"Novel insights into mesothelioma biology and implications for therapy","volume":"17","author":"Yap","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.48286\/aro.2021.20","article-title":"Malignant Mesothelioma in the Italian Region Emilia-Romagna: Incidence and Asbestos exposure update to 2020","volume":"1","author":"Mangone","year":"2021","journal-title":"Ann. Res. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Barbarino, M., and Giordano, A. (2021). Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System. Cancers, 13.","DOI":"10.3390\/cancers13061318"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1002\/1097-0142(19850501)55:9<1968::AID-CNCR2820550923>3.0.CO;2-9","article-title":"Malignant Mesothelioma Secondary to Chronic Inflammation and Old Scars. Two New Cases and Review of the Literature","volume":"55","author":"Hillerdal","year":"1985","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng.3520","article-title":"Comprehensive Genomic Analysis of Malignant Pleural Mesothelioma Identifies Recurrent Mutations, Gene Fusions and Splicing Alterations","volume":"48","author":"Bueno","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fonc.2020.00101","article-title":"Preclinical Models of Malignant Mesothelioma","volume":"10","author":"Testa","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5858\/arpa.2017-0124-RA","article-title":"Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group","volume":"142","author":"Husain","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_10","first-page":"2108","article-title":"Homozygous Deletion of CDKN2A and Codeletion of the Methylthioadenosine Phosphorylase Gene in the Majority of Pleural Mesotheliomas","volume":"9","author":"Illei","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"627","DOI":"10.4161\/cbt.11.7.14948","article-title":"Targeting Tumors That Lack Methylthioadenosine Phosphorylase (MTAP) Activity: Current Strategies","volume":"11","author":"Bertino","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ajpath.2010.11.059","article-title":"Down-Regulation of Methylthioadenosine Phosphorylase (MTAP) Induces Progression of Hepatocellular Carcinoma via Accumulation of 5\u2032-Deoxy-5\u2032-Methylthioadenosine (MTA)","volume":"178","author":"Kirovski","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3322\/caac.21572","article-title":"Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy","volume":"69","author":"Carbone","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/gcc.2870090114","article-title":"Deletion Mapping of the Short Arm of Chromosome 3 in Human Malignant Mesothelioma","volume":"9","author":"Lu","year":"1994","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1158\/2159-8290.CD-18-0804","article-title":"Integrative Molecular Characterization of Malignant Pleural Mesothelioma","volume":"8","author":"Hmeljak","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"579327","DOI":"10.3389\/fonc.2020.579327","article-title":"CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation","volume":"10","author":"Cheng","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.lungcan.2008.08.014","article-title":"Functional Inactivation of NF2\/Merlin in Human Mesothelioma","volume":"64","author":"Thurneysen","year":"2009","journal-title":"Lung Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yang, H., Hall, S., Sun, B., Zhao, L., Gao, Y., Schmid, R.A., Tan, S.T., Peng, R.W., and Yao, F. (2021). NF2 and Canonical Hippo-YAP Pathway Define Distinct Tumor Subsets Characterized by Different Immune Deficiency and Treatment Implications in Human Pleural Mesothelioma. Cancers, 13.","DOI":"10.3390\/cancers13071561"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20191257","DOI":"10.1084\/jem.20191257","article-title":"Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice","volume":"217","author":"Badhai","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"653497","DOI":"10.3389\/fonc.2021.653497","article-title":"P14\/ARF-Positive Malignant Pleural Mesothelioma: A Phenotype with Distinct Immune Microenvironment","volume":"11","author":"Pezzuto","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1038\/s41467-021-21798-w","article-title":"Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch Repair Deficiency Predicts Response of Solid Tumors to PD-1 Blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1007\/s12094-019-02275-9","article-title":"Analysis of Mismatch Repair (MMR) Proteins Expression in a Series of Malignant Pleural Mesothelioma (MPM) Patients","volume":"22","author":"Iranzo","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/CCO.0000000000000697","article-title":"Malignant Pleural Mesothelioma: Recent Developments","volume":"33","author":"Sinn","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3389\/fonc.2020.01742","article-title":"The Use of Immunohistochemistry, Fluorescence in Situ Hybridization, and Emerging Epigenetic Markers in the Diagnosis of Malignant Pleural Mesothelioma (MPM): A Review","volume":"10","author":"Rozitis","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3389\/fonc.2020.00445","article-title":"Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and Critical Evaluation","volume":"10","author":"Ferrari","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"350","DOI":"10.21037\/tlcr.2017.06.06","article-title":"Targeting the Epigenome in Malignant Pleural Mesothelioma","volume":"6","author":"McLoughlin","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16848","DOI":"10.18632\/oncotarget.4253","article-title":"Reactive oxygen species a double-edged sword for mesothelioma","volume":"6","author":"Benedetti","year":"2015","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.ajpath.2012.12.028","article-title":"New insights into understanding the mechanisms, pathogenesis, and management of malignant mesotheliomas","volume":"182","author":"Mossman","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Minnema-Luiting, J., Vroman, H., Aerts, J., and Cornelissen, R. (2018). Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041041"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jtho.2017.09.1968","article-title":"Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma","volume":"13","author":"Patil","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1093\/annonc\/mdy086","article-title":"Malignant pleural mesothelioma immune microenvironment and checkpoint expression: Correlation with clinical-pathological features and intratumor heterogeneity over time","volume":"29","author":"Pasello","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_35","first-page":"516","article-title":"Inflammation in malignant mesothelioma\u2014Friend or foe?","volume":"1","author":"Linton","year":"2012","journal-title":"Annal. Cardiothorac. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3389\/fonc.2019.01366","article-title":"The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy","volume":"9","author":"Chu","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cornelissen, R., Lievense, L.A., Maat, A.P., Hendriks, R.W., Hoogsteden, H.C., Bogers, A.J., Hegmans, J.P., and Aerts, J.G. (2014). Ratio of intratumoral macrophage phenotypes is a prognostic factor in epithelioid malignant pleural mesothelioma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106742"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59R","DOI":"10.1203\/01.pdr.0000203592.04530.06","article-title":"Cancer stem cells","volume":"59","author":"Guo","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.gene.2018.09.052","article-title":"Cancer stem cells: A brief review of the current status","volume":"681","year":"2019","journal-title":"Gene"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pasdar, E.A., Smits, M., Stapelberg, M., Bajzikova, M., Stantic, M., Goodwin, J., Yan, B., Stursa, J., Kovarova, J., and Sachaphibulkij, K. (2015). Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119549"},{"key":"ref_41","first-page":"437","article-title":"Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed","volume":"37","author":"Carboni","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Oehl, K., Vrugt, B., Opitz, I., and Meerang, M. (2018). Heterogeneity in Malignant Pleural Mesothelioma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061603"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4779","DOI":"10.1111\/febs.13023","article-title":"Cancer stem cells--important players in tumor therapy resistance","volume":"281","author":"Colak","year":"2014","journal-title":"FEBS J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.lungcan.2010.04.020","article-title":"Characterization of side population cells in human malignant mesothelioma cell lines","volume":"70","author":"Kai","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.stemcr.2017.02.005","article-title":"Stem Cell Factor-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells","volume":"8","author":"Blum","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Begicevic, R.R., and Falasca, M. (2017). ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112362"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cortes-Dericks, L., Froment, L., Boesch, R., Schmid, R.A., and Karoubi, G. (2014). Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) phenotype and sphere-forming capacity. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-304"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ijc.32419","article-title":"Wnt\/IL-1\u03b2\/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5","volume":"146","author":"Milosevic","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1038\/onc.2011.485","article-title":"SASP mediates chemoresistance and tumor-initiating-activity of mesothelioma cells","volume":"31","author":"Canino","year":"2012","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1158\/0008-5472.CAN-13-2062","article-title":"Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis","volume":"74","author":"Menges","year":"2014","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"237ra68","DOI":"10.1126\/scitranslmed.3008639","article-title":"Merlin deficiency predicts FAK inhibitor sensitivity: A synthetic lethal relationship","volume":"6","author":"Shapiro","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"51733","DOI":"10.18632\/oncotarget.18517","article-title":"Inhibition of FAK kinase activity preferentially targets cancer stem cells","volume":"8","author":"Kolev","year":"2017","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12929-018-0426-4","article-title":"Cancer stem cells as key drivers of tumour progression","volume":"25","author":"Ayob","year":"2018","journal-title":"J. Biom. Sci."},{"key":"ref_54","first-page":"2153","article-title":"SDF1\/CXCL12 is involved in recruitment of stem-like progenitor cells to orthotopic murine malignant mesothelioma spheroids","volume":"30","author":"Lau","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"34495","DOI":"10.18632\/oncotarget.26130","article-title":"Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation","volume":"9","author":"Adhikary","year":"2018","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1158\/1541-7786.MCR-19-0914","article-title":"The YAP1 Signaling Inhibitors, Verteporfin and CA3, Suppress the Mesothelioma Cancer Stem Cell Phenotype","volume":"18","author":"Kandasamy","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1158\/0008-5472.CAN-18-3962","article-title":"The Tumor Microenvironment Innately Modulates Cancer Progression","volume":"79","author":"Hinshaw","year":"2019","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/PPO.0000000000000127","article-title":"The Role of Stroma in Tumor Development","volume":"21","author":"Werb","year":"2015","journal-title":"Cancer J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/JTO.0b013e3181f8a1bd","article-title":"The role of tumor stroma in cancer progression and prognosis: Emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer","volume":"6","author":"Bremnes","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Napoli, F., List\u00ec, A., Zambelli, V., Witel, G., Bironzo, P., Papotti, M., Volante, M., Scagliotti, G., and Righi, L. (2021). Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma. Cancers, 13.","DOI":"10.3390\/cancers13112564"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jtho.2016.06.021","article-title":"Pleural Effusion of Patients with Malignant Mesothelioma Induces Macrophage-Mediated T Cell Suppression","volume":"11","author":"Lievense","year":"2016","journal-title":"J. Thorac. Onc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1084\/jem.20111653","article-title":"TGF-\u03b2 synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth","volume":"209","author":"Fujii","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s11373-008-9264-9","article-title":"Connective tissue growth factor (CTGF) and cancer progression","volume":"15","author":"Chu","year":"2008","journal-title":"J. Biomed. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jang, I., and Beningo, K.A. (2019). Integrins, CAFs and Mechanical Forces in the Progression of Cancer. Cancers, 11.","DOI":"10.3390\/cancers11050721"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"838","DOI":"10.3892\/or.2020.7669","article-title":"Connective tissue growth factor produced by cancer-associated fibroblasts correlates with poor prognosis in epithelioid malignant pleural mesothelioma","volume":"44","author":"Ohara","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/j.ajpath.2011.05.060","article-title":"Pleural mesothelioma instigates tumor-associated fibroblasts to promote progression via a malignant cytokine network","volume":"179","author":"Li","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<72::AID-PATH401>3.0.CO;2-0","article-title":"Angiogenic cytokines in mesothelioma: A study of VEGF, FGF-1 and -2, and TGF beta expression","volume":"189","author":"Weyler","year":"1999","journal-title":"J. Pathol."},{"key":"ref_68","first-page":"3055","article-title":"Cancer-associated fibroblast regulation of tumor neo-angiogenesis as a therapeutic target in cancer","volume":"17","author":"Wang","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lungcan.2020.09.022","article-title":"Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort","volume":"150","author":"Chia","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1183\/09031936.06.00135305","article-title":"Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses","volume":"27","author":"Hegmans","year":"2006","journal-title":"Eur. Resp. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1009285","DOI":"10.1080\/2162402X.2015.1009285","article-title":"The tumoral and stromal immune microenvironment in malignant pleural mesothelioma: A comprehensive analysis reveals prognostic immune markers","volume":"4","author":"Ujiie","year":"2015","journal-title":"Oncoimmunology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"89722","DOI":"10.18632\/oncotarget.21113","article-title":"Abundant expression of TIM-3, LAG-3, PD-1 and PD-L1 as immunotherapy checkpoint targets in effusions of mesothelioma patients","volume":"8","author":"Marcq","year":"2017","journal-title":"Oncotarget"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"111ra120","DOI":"10.1126\/scitranslmed.3003130","article-title":"The PDL1-PD1 axis converts human TH1 cells into regulatory T cells","volume":"3","author":"Amarnath","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e1638211","DOI":"10.1080\/2162402X.2019.1638211","article-title":"Phenotypic and functional analysis of malignant mesothelioma tumor-infiltrating lymphocytes","volume":"8","author":"Klampatsa","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.jtcvs.2007.10.026","article-title":"Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma","volume":"135","author":"Anraku","year":"2008","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s00262-010-0881-6","article-title":"CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection","volume":"59","author":"Yamada","year":"2010","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"660039","DOI":"10.3389\/fonc.2021.660039","article-title":"Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma","volume":"11","author":"Hiltbrunner","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hirayama, D., Iida, T., and Nakase, H. (2017). The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010092"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1053\/j.semdp.2006.08.002","article-title":"The pathogenesis of mesothelioma","volume":"23","author":"Carbone","year":"2006","journal-title":"Semin. Diagn. Path."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"D\u00e9sage, A.L., Karpathiou, G., Peoc\u2019h, M., and Froudarakis, M.E. (2021). The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review. Cancers, 13.","DOI":"10.3390\/cancers13133205"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1089\/ars.2019.7818","article-title":"The Role of HMGB1, a Nuclear Damage-Associated Molecular Pattern Molecule, in the Pathogenesis of Lung Diseases","volume":"31","author":"Wang","year":"2019","journal-title":"Antiox. Redox Signal."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"238","DOI":"10.21037\/atm.2017.04.29","article-title":"Mesothelioma: Recent highlights","volume":"5","author":"Carbone","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12989-016-0127-7","article-title":"Multi-walled carbon nanotube induces nitrative DNA damage in human lung epithelial cells via HMGB1-RAGE interaction and Toll-like receptor 9 activation","volume":"13","author":"Hiraku","year":"2016","journal-title":"Part. Fibre Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.tiv.2015.06.012","article-title":"Multi-walled carbon nanotube induced frustrated phagocytosis, cytotoxicity and pro-inflammatory conditions in macrophages are length dependent and greater than that of asbestos","volume":"29","author":"Boyles","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1158\/1078-0432.CCR-11-2259","article-title":"Molecular pathways: Targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma","volume":"18","author":"Carbone","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_86","first-page":"e1373235","article-title":"The \u201cdon\u2019t eat me\u201d signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma","volume":"7","author":"Forster","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Cersosimo, F., Lonardi, S., Bernardini, G., Telfer, B., Mandelli, G.E., Santucci, A., Vermi, W., and Giurisato, E. (2020). Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155207"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/eji.201141670","article-title":"Regulators of macrophage activation","volume":"41","author":"Martinez","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_89","first-page":"4107","article-title":"Tumor-associated macrophages in lung cancer: Friend or foe? (Review)","volume":"22","author":"Xu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/j.apsb.2020.04.004","article-title":"The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy","volume":"10","author":"Yang","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Colin, D.J., Cottet-Dumoulin, D., Faivre, A., Germain, S., Triponez, F., and Serre-Beinier, V. (2018). Experimental Model of Human Malignant Mesothelioma in Athymic Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071881"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.jtho.2016.06.022","article-title":"Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages","volume":"11","author":"Blondy","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Sarode, P., Schaefer, M.B., Grimminger, F., Seeger, W., and Savai, R. Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk. Front. Oncol., 2020. 10, 324.","DOI":"10.3389\/fonc.2020.00324"},{"key":"ref_94","first-page":"543","article-title":"Differential effects of malignant mesothelioma cells on THP-1 monocytes and macrophages","volume":"34","author":"Izzi","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5234","DOI":"10.1002\/cncr.26143","article-title":"Circulating and tumor-infiltrating myeloid cells predict survival in human pleural mesothelioma","volume":"117","author":"Burt","year":"2011","journal-title":"Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1111\/cas.14523","article-title":"Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma","volume":"111","author":"Horio","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12929-019-0568-z","article-title":"Tumor-associated macrophages: An accomplice in solid tumor progression","volume":"26","author":"Chen","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e000182","DOI":"10.1136\/jitc-2019-000182","article-title":"Involvement of the M-CSF\/IL-34\/CSF-1R pathway in malignant pleural mesothelioma","volume":"8","author":"Blondy","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e1167","DOI":"10.1038\/cddis.2014.136","article-title":"Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT activation","volume":"5","author":"Cioce","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1158\/2326-6066.CIR-16-0309","article-title":"Depletion of Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy","volume":"5","author":"Dammeijer","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Magkouta, S.F., Vaitsi, P.C., Pappas, A.G., Iliopoulou, M., Kosti, C.N., Psarra, K., and Kalomenidis, I.T. (2021). CSF1\/CSF1R Axis Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1 Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13112546"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.ccr.2014.05.016","article-title":"Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy","volume":"25","author":"Ries","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: From mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1158\/1535-7163.MCT-07-0579","article-title":"Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma","volume":"7","author":"Miselis","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/sj.bjc.6605814","article-title":"Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma","volume":"103","author":"Veltman","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.smim.2017.09.004","article-title":"Targeting tumor associated macrophages: The new challenge for nanomedicine","volume":"34","author":"Digifico","year":"2017","journal-title":"Semin. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1158\/0008-5472.CAN-19-2416","article-title":"Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis","volume":"80","author":"Giurisato","year":"2020","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coph.2016.04.001","article-title":"Immunosuppressive activities of adenosine in cancer","volume":"29","author":"Allard","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1586\/14737159.2015.1071666","article-title":"The potential of tumor-derived exosomes for noninvasive cancer monitoring","volume":"15","author":"Whiteside","year":"2015","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/imr.12528","article-title":"The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets","volume":"276","author":"Allard","year":"2017","journal-title":"Immunol Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/14728222.2019.1559829","article-title":"CD73 as a potential opportunity for cancer immunotherapy","volume":"23","author":"Ghalamfarsa","year":"2019","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00109-014-1189-3","article-title":"Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1\u03b1-dependent and extracellular adenosine-mediated tumor protection","volume":"92","author":"Hatfield","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1182\/blood-2008-02-136325","article-title":"Adenosine receptors in regulation of dendritic cell differentiation and function","volume":"112","author":"Novitskiy","year":"2008","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1084\/jem.20062512","article-title":"Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression","volume":"204","author":"Deaglio","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Reyna-Jeldes, M., D\u00edaz-Mu\u00f1oz, M., Madariaga, J.A., Coddou, C., and V\u00e1zquez-Cuevas, F.G. (2021). Autocrine and paracrine purinergic signaling in the most lethal types of cancer. Purinergic Signal., 1\u201326.","DOI":"10.1007\/s11302-021-09785-8"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Yang, H., Yao, F., Davis, P.F., Tan, S.T., and Hall, S. (2021). CD73, Tumor Plasticity and Immune Evasion in Solid Cancers. Cancers, 13.","DOI":"10.3390\/cancers13020177"},{"key":"ref_117","first-page":"e1268308","article-title":"Prostaglandin E2-mediated adenosinergic effects on CD14+ cells: Self-amplifying immunosuppression in cancer","volume":"6","author":"Salimu","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1161\/ATVBAHA.111.226852","article-title":"Regulation of macrophage function by adenosine","volume":"32","author":"Pacher","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbrc.2010.01.023","article-title":"Adenosine up-regulates vascular endothelial growth factor in human macrophages","volume":"392","author":"Ernens","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7250","DOI":"10.1158\/0008-5472.CAN-13-3583","article-title":"Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment","volume":"74","author":"Cekic","year":"2014","journal-title":"Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"676","DOI":"10.4049\/jimmunol.1003884","article-title":"Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production","volume":"187","author":"Clayton","year":"2011","journal-title":"J. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0002-9440(10)63698-X","article-title":"An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors","volume":"163","author":"Ramanathan","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1182\/blood-2007-01-065870","article-title":"A2A adenosine receptors and C\/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli","volume":"110","author":"Gergely","year":"2007","journal-title":"Blood"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1096\/fj.99-0508com","article-title":"Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms","volume":"14","author":"Kuhel","year":"2000","journal-title":"FASEB J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1124\/jpet.105.096016","article-title":"Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor","volume":"317","author":"Kreckler","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8260","DOI":"10.4049\/jimmunol.175.12.8260","article-title":"Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism","volume":"175","author":"Lutz","year":"2005","journal-title":"J. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1096\/fj.11-190934","article-title":"Adenosine promotes alternative macrophage activation via A2A and A2B receptors","volume":"26","author":"Selmeczy","year":"2012","journal-title":"FASEB J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jhep.2020.10.021","article-title":"Tumor-derived adenosine promotes macrophage proliferation in human hepatocellular carcinoma","volume":"74","author":"Wang","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/s41467-019-09307-6","article-title":"Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications","volume":"10","author":"Blum","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e98575","DOI":"10.1172\/jci.insight.98575","article-title":"Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma","volume":"3","author":"Lee","year":"2018","journal-title":"JCI Insight"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"684025","DOI":"10.3389\/fonc.2021.684025","article-title":"Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma","volume":"11","author":"Wadowski","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jtho.2017.02.013","article-title":"The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma","volume":"12","author":"Thapa","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41379-019-0364-z","article-title":"V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma","volume":"33","author":"Muller","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1758835920971421","DOI":"10.1177\/1758835920971421","article-title":"Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma","volume":"12","author":"Yang","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ebiom.2019.09.003","article-title":"Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions","volume":"48","author":"Alcala","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Tazzari, M., Brich, S., Tuccitto, A., Bozzi, F., Beretta, V., Spagnuolo, R.D., Negri, T., Stacchiotti, S., Deraco, M., and Baratti, D. (2018). Complex Immune Contextures Characterise Malignant Peritoneal Mesothelioma: Loss of Adaptive Immunological Signature in the More Aggressive Histological Types. J. Immunol. Res., 5804230.","DOI":"10.1155\/2018\/5804230"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e001601","DOI":"10.1136\/jitc-2020-001601","article-title":"Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification","volume":"9","author":"Alay","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature12626","article-title":"Influence of tumour micro-environment heterogeneity on therapeutic response","volume":"501","author":"Junttila","year":"2013","journal-title":"Nature"},{"key":"ref_139","first-page":"51","article-title":"New and emerging therapeutic options for malignant pleural mesothelioma: Review of early clinical trials","volume":"7","author":"Kotova","year":"2015","journal-title":"Cancer Manag. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.critrevonc.2016.08.011","article-title":"The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?","volume":"107","author":"Bronte","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s00262-011-1103-6","article-title":"Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma","volume":"60","author":"Bograd","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1080\/14737140.2016.1244008","article-title":"Targeting the vasculature: Anti-angiogenic agents for malignant mesothelioma","volume":"16","author":"Chia","year":"2016","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.jtho.2018.08.2036","article-title":"Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation","volume":"13","author":"Tsao","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1200\/JCO.2017.72.9012","article-title":"Nintedanib Plus Pemetrexed\/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial","volume":"35","author":"Grosso","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7583","DOI":"10.1200\/jco.2014.32.15_suppl.7583","article-title":"Dendritic cell vaccination in malignant pleural mesothelioma: A phase I\/II study","volume":"32","author":"Berneman","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e1474318","DOI":"10.1080\/2162402X.2018.1474318","article-title":"Low-dose cyclophosphamide depletes circulating na\u00efve and activated regulatory T cells in malignant pleural mesothelioma patients synergistically treated with dendritic cell-based immunotherapy","volume":"7","author":"Noordam","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3389\/fonc.2019.01519","article-title":"Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future","volume":"9","author":"Nicolini","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_148","first-page":"1","article-title":"Biological basis for novel mesothelioma therapies","volume":"10","author":"Obacz","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"102815","DOI":"10.1016\/j.critrevonc.2019.102815","article-title":"Emerging therapies in malignant pleural mesothelioma","volume":"144","author":"Cinausero","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"S100","DOI":"10.21037\/tlcr.2019.11.23","article-title":"Immunotherapy for mesothelioma: A critical review of current clinical trials and future perspectives","volume":"9","author":"Gray","year":"2020","journal-title":"Trans. Lung Cancer Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.omto.2020.01.009","article-title":"Antimesothelioma Immunotherapy by CTLA-4 Blockade Depends on Active PD1-Based TWIST1 Vaccination","volume":"16","author":"Tan","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_152","first-page":"192","article-title":"Current Advances in CAR T Cell Therapy for Malignant Mesothelioma","volume":"2","author":"Klampatsa","year":"2020","journal-title":"J. Cell. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1093\/annonc\/mdz163","article-title":"Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced\/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages","volume":"30","author":"Italiano","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.jtho.2019.12.128","article-title":"Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus","volume":"15","author":"Delaunay","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e111","DOI":"10.1016\/j.jtho.2020.03.007","article-title":"Oncolytic Viral Therapy for Malignant Pleural Mesothelioma","volume":"15","author":"Yang","year":"2020","journal-title":"J. Thorac. 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