{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:35:08Z","timestamp":1790976908520,"version":"4.1.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["jto.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thoracic Oncology"],"published-print":{"date-parts":[[2018,1]]},"DOI":"10.1016\/j.jtho.2017.09.1968","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T13:01:35Z","timestamp":1508850095000},"page":"124-133","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":57,"title":["Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma"],"prefix":"10.1016","volume":"13","author":[{"given":"Namrata S.","family":"Patil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisella","family":"Righi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Koeppen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Izzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Libener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Loiacono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Monica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Buttigliero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Novello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti S.","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Papotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kowanetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio V.","family":"Scagliotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtho.2017.09.1968_bib1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.lungcan.2015.05.014","article-title":"Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England","volume":"89","author":"Damhuis","year":"2015","journal-title":"Lung Cancer"},{"key":"10.1016\/j.jtho.2017.09.1968_bib2","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2217\/fon.12.14","article-title":"Systemic treatment of malignant pleural mesothelioma","volume":"8","author":"Grosso","year":"2012","journal-title":"Future Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib4","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ctrv.2015.05.001","article-title":"The established and future biomarkers of malignant pleural mesothelioma","volume":"41","author":"Panou","year":"2015","journal-title":"Cancer Treat Rev"},{"key":"10.1016\/j.jtho.2017.09.1968_bib5","series-title":"Tumours of the Lung, Pleura, Thymus and Heart","year":"2015"},{"key":"10.1016\/j.jtho.2017.09.1968_bib6","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1200\/JCO.2009.25.9275","article-title":"Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy","volume":"28","author":"Righi","year":"2010","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib7","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.jtho.2016.05.020","article-title":"The genetic landscape of malignant pleural mesothelioma: results from massively parallel sequencing","volume":"11","author":"Hylebos","year":"2016","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib8","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":"10.1016\/j.jtho.2017.09.1968_bib9","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1158\/1078-0432.CCR-13-2429","article-title":"Molecular classification of malignant pleural mesothelioma: identification of a poor prognosis subgroup linked to the epithelial-to-mesenchymal transition","volume":"20","author":"de Reynies","year":"2014","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtho.2017.09.1968_bib10","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/cdd.2015.165","article-title":"Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease","volume":"23","author":"Chernova","year":"2016","journal-title":"Cell Death Differ"},{"key":"10.1016\/j.jtho.2017.09.1968_bib11","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1158\/0008-5472.CAN-14-1008","article-title":"Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma","volume":"75","author":"Guo","year":"2015","journal-title":"Cancer Res"},{"key":"10.1016\/j.jtho.2017.09.1968_bib12","doi-asserted-by":"crossref","first-page":"18713","DOI":"10.18632\/oncotarget.7666","article-title":"microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma","volume":"7","author":"Walter","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.jtho.2017.09.1968_bib13","first-page":"1915","article-title":"Screening of pleural mesotheliomas for DNA-damage repair players by digital gene expression analysis can enhance clinical management of patients receiving platin-based chemotherapy","volume":"7","author":"Walter","year":"2016","journal-title":"J\u00a0Cancer"},{"key":"10.1016\/j.jtho.2017.09.1968_bib14","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.ctrv.2015.09.006","article-title":"Targeting immune checkpoints: new opportunity for mesothelioma treatment?","volume":"41","author":"Marcq","year":"2015","journal-title":"Cancer Treat Rev"},{"key":"10.1016\/j.jtho.2017.09.1968_bib15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.critrevonc.2016.02.001","article-title":"PD-L1 expression in cancer patients receiving anti PD-1\/PD-L1 antibodies: a\u00a0systematic review and meta-analysis","volume":"100","author":"Gandini","year":"2016","journal-title":"Crit Rev Oncol Hematol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib16","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jtho.2017.09.1968_bib17","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1200\/JCO.2014.59.0703","article-title":"Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial","volume":"33","author":"Motzer","year":"2015","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib18","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for recurrent squamous-cell carcinoma of the head and neck","volume":"375","author":"Ferris","year":"2016","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jtho.2017.09.1968_bib19","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/17425255.2017.1277204","article-title":"Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma","volume":"13","author":"Patel","year":"2017","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib20","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.jtho.2017.09.1968_bib21","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/S0140-6736(16)00587-0","article-title":"Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial","volume":"387","author":"Fehrenbacher","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.jtho.2017.09.1968_bib22","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1200\/JCO.2015.63.7421","article-title":"Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study","volume":"34","author":"McDermott","year":"2016","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib23","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0140-6736(16)32517-X","article-title":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial","volume":"389","author":"Rittmeyer","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jtho.2017.09.1968_bib24","doi-asserted-by":"crossref","first-page":"e0121071","DOI":"10.1371\/journal.pone.0121071","article-title":"Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM)","volume":"10","author":"Cedres","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.jtho.2017.09.1968_bib25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.humpath.2016.01.010","article-title":"Immune biomarkers PD-1\/PD-L1 and TLR3 in malignant pleural mesotheliomas","volume":"52","author":"Combaz-Lair","year":"2016","journal-title":"Hum Pathol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib26","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.jtho.2016.07.033","article-title":"Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab","volume":"11","author":"Khanna","year":"2016","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib27","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1097\/JTO.0000000000000436","article-title":"Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study","volume":"10","author":"Lo Iacono","year":"2015","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/0471142727.mb25b10s94","article-title":"Digital multiplexed gene expression analysis using the NanoString nCounter system","author":"Kulkarni","year":"2011","journal-title":"Curr Protoc Mol Biol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib29","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":"10.1016\/j.jtho.2017.09.1968_bib30","first-page":"492608","article-title":"Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis","volume":"2012","author":"Matsuzaki","year":"2012","journal-title":"J\u00a0Biomed Biotechnol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib31","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1165\/rcmb.2013-0472TR","article-title":"Immunotherapy for malignant pleural mesothelioma. Current status and future prospects","volume":"50","author":"Wong","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib32","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1097\/JTO.0000000000000177","article-title":"B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis","volume":"9","author":"Mansfield","year":"2014","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib33","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1158\/1078-0432.CCR-16-0066","article-title":"Genomic approaches to understanding response and resistance to immunotherapy","volume":"22","author":"Braun","year":"2016","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtho.2017.09.1968_bib34","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ng.855","article-title":"The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma","volume":"43","author":"Bott","year":"2011","journal-title":"Nat Genet"},{"key":"10.1016\/j.jtho.2017.09.1968_bib35","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1158\/1078-0432.CCR-15-1507","article-title":"The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition","volume":"22","author":"Hegde","year":"2016","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtho.2017.09.1968_bib36","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/icb.2010.88","article-title":"CD40-activated B cells contribute to mesothelioma tumor regression","volume":"89","author":"Jackaman","year":"2011","journal-title":"Immunol Cell Biol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib37","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1165\/rcmb.2010-0435OC","article-title":"Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients","volume":"45","author":"Maeda","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib38","doi-asserted-by":"crossref","first-page":"302649","DOI":"10.1155\/2015\/302649","article-title":"Expression of ribonucleotide reductase subunit-2 and thymidylate synthase correlates with poor prognosis in patients with resected stages I-III non-small cell lung cancer","volume":"2015","author":"Grossi","year":"2015","journal-title":"Dis Markers"},{"key":"10.1016\/j.jtho.2017.09.1968_bib39","doi-asserted-by":"crossref","first-page":"12679","DOI":"10.1007\/s13277-014-2592-7","article-title":"Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy","volume":"35","author":"Zhao","year":"2014","journal-title":"Tumour Biol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib40","doi-asserted-by":"crossref","first-page":"e0127600","DOI":"10.1371\/journal.pone.0127600","article-title":"Ribonucleotide reductase subunit M2 predicts survival in subgroups of patients with non-small cell lung carcinoma: effects of gender and smoking status","volume":"10","author":"Mah","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.jtho.2017.09.1968_bib41","first-page":"3375","article-title":"Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis","volume":"19","author":"Zhou","year":"2015","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"10.1016\/j.jtho.2017.09.1968_bib42","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\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtho.2017.09.1968_bib43","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1158\/2326-6066.CIR-16-0171","article-title":"Cytotoxic T cells in PD-L1-positive malignant pleural mesotheliomas are counterbalanced by distinct immunosuppressive factors","volume":"4","author":"Awad","year":"2016","journal-title":"Cancer Immunol Res"}],"container-title":["Journal of Thoracic Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1556086417327909?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1556086417327909?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T21:22:47Z","timestamp":1546291367000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1556086417327909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["S1556086417327909"],"URL":"https:\/\/doi.org\/10.1016\/j.jtho.2017.09.1968","relation":{},"ISSN":["1556-0864"],"issn-type":[{"value":"1556-0864","type":"print"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma","name":"articletitle","label":"Article Title"},{"value":"Journal of Thoracic Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtho.2017.09.1968","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}