{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:56:30Z","timestamp":1782255390795,"version":"3.54.5"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and\/or systemic immunosuppressive factors, thus creating a host environment more amenable to immunotherapy. This article reviews the immunotherapeutic approaches being evaluated in patients with MPM and discusses how immunotherapy might be rationally combined with conventional tumor cytoreductive therapies for this disease.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0472tr","type":"journal-article","created":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T14:45:38Z","timestamp":1398955538000},"page":"870-875","source":"Crossref","is-referenced-by-count":20,"title":["Immunotherapy for Malignant Pleural Mesothelioma. Current Status and Future Prospects"],"prefix":"10.1093","volume":"50","author":[{"given":"Raymond M.","family":"Wong","sequence":"first","affiliation":[{"name":"Pacific Meso Center at the Pacific Heart, Lung & Blood Institute, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Ianculescu","sequence":"additional","affiliation":[{"name":"Pacific Meso Center at the Pacific Heart, Lung & Blood Institute, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherven","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Pulmonary and Critical Care"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L.","family":"Gage","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M.","family":"Olevsky","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Kotova","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko N.","family":"Kostic","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Grundfest","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Comprehensive Mesothelioma Program, University of California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and"},{"name":"Division of Thoracic Surgery and Comprehensive Mesothelioma Program, University of California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2026030623184350400_bib1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0013-9351(88)80061-6","article-title":"Asbestos exposure indices","volume":"46","author":"Lippmann","year":"1988","journal-title":"Environ Res"},{"key":"2026030623184350400_bib2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ccm.2012.12.005","article-title":"Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies","volume":"34","author":"Haas","year":"2013","journal-title":"Clin Chest Med"},{"key":"2026030623184350400_bib3","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 Clin Oncol"},{"key":"2026030623184350400_bib4","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/(SICI)1097-0142(19981115)83:10<2099::AID-CNCR8>3.0.CO;2-3","article-title":"Intrapleural administration of interleukin-2 for the treatment of patients with malignant pleural mesothelioma: a Phase II study","volume":"83","author":"Astoul","year":"1998","journal-title":"Cancer"},{"key":"2026030623184350400_bib5","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":"2026030623184350400_bib6","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1002\/1097-0142(19941101)74:9<2460::AID-CNCR2820740912>3.0.CO;2-N","article-title":"Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma","volume":"74","author":"Boutin","year":"1994","journal-title":"Cancer"},{"key":"2026030623184350400_bib7","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1158\/1078-0432.CCR-07-0403","article-title":"A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses","volume":"13","author":"Sterman","year":"2007","journal-title":"Clin Cancer Res"},{"key":"2026030623184350400_bib8","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/mt.2009.309","article-title":"A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions","volume":"18","author":"Sterman","year":"2010","journal-title":"Mol Ther"},{"key":"2026030623184350400_bib9","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1164\/rccm.201103-0554CR","article-title":"A trial of intrapleural adenoviral-mediated Interferon-\u03b12b gene transfer for malignant pleural mesothelioma","volume":"184","author":"Sterman","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030623184350400_bib10","doi-asserted-by":"crossref","first-page":"208ra147","DOI":"10.1126\/scitranslmed.3006941","article-title":"Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression","volume":"5","author":"Hassan","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026030623184350400_bib11","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1164\/rccm.200909-1465OC","article-title":"Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma","volume":"181","author":"Hegmans","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030623184350400_bib12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.lungcan.2006.01.007","article-title":"Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma","volume":"52","author":"Powell","year":"2006","journal-title":"Lung Cancer"},{"key":"2026030623184350400_bib13","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s00262-010-0871-8","article-title":"WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer","volume":"59","author":"Krug","year":"2010","journal-title":"Cancer Immunol Immunother"},{"key":"2026030623184350400_bib14","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1073\/pnas.0813101106","article-title":"Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains","volume":"106","author":"Carpenito","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026030623184350400_bib15","doi-asserted-by":"crossref","first-page":"9053","DOI":"10.1158\/0008-5472.CAN-10-2880","article-title":"Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor","volume":"70","author":"Zhao","year":"2010","journal-title":"Cancer Res"},{"key":"2026030623184350400_bib16","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1158\/1078-0432.CCR-11-0351","article-title":"Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor","volume":"17","author":"Moon","year":"2011","journal-title":"Clin Cancer Res"},{"key":"2026030623184350400_bib17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1479-5876-11-187","article-title":"Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells","volume":"11","author":"Schuberth","year":"2013","journal-title":"J Transl Med"},{"key":"2026030623184350400_bib18","doi-asserted-by":"crossref","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","article-title":"T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia","volume":"3","author":"Kalos","year":"2011","journal-title":"Sci Transl Med"},{"key":"2026030623184350400_bib19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-med-060512-150254","article-title":"Chimeric antigen receptor therapy for cancer","volume":"65","author":"Barrett","year":"2014","journal-title":"Annu Rev Med"},{"key":"2026030623184350400_bib20","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1126\/science.271.5256.1734","article-title":"Enhancement of antitumor immunity by CTLA-4 blockade","volume":"271","author":"Leach","year":"1996","journal-title":"Science"},{"key":"2026030623184350400_bib21","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1084\/jem.190.3.355","article-title":"Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte\/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation","volume":"190","author":"van Elsas","year":"1999","journal-title":"J Exp Med"},{"key":"2026030623184350400_bib22","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/S1470-2045(13)70381-4","article-title":"Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial","volume":"14","author":"Calabr\u00f2","year":"2013","journal-title":"Lancet Oncol"},{"key":"2026030623184350400_bib23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12180","article-title":"Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma","volume":"1291","author":"Wolchok","year":"2013","journal-title":"Ann N Y Acad Sci"},{"key":"2026030623184350400_bib24","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/pros.21020","article-title":"Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+","volume":"69","author":"Sfanos","year":"2009","journal-title":"Prostate"},{"key":"2026030623184350400_bib25","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1182\/blood-2008-12-195792","article-title":"Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh","year":"2009","journal-title":"Blood"},{"key":"2026030623184350400_bib26","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nri2326","article-title":"Inhibitory B7-family molecules in the tumour microenvironment","volume":"8","author":"Zou","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2026030623184350400_bib27","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"2026030623184350400_bib28","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1158\/1078-0432.CCR-12-2625","article-title":"Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody","volume":"19","author":"Lipson","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2026030623184350400_bib29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1056\/NEJMoa1305133","article-title":"Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma","volume":"369","author":"Hamid","year":"2013","journal-title":"N Engl J Med"},{"key":"2026030623184350400_bib30","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","volume":"366","author":"Brahmer","year":"2012","journal-title":"N Engl J Med"},{"key":"2026030623184350400_bib31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1056\/NEJMoa1302369","article-title":"Nivolumab plus ipilimumab in advanced melanoma","volume":"369","author":"Wolchok","year":"2013","journal-title":"N Engl J Med"},{"key":"2026030623184350400_bib32","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 Respir J"},{"key":"2026030623184350400_bib33","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":"2026030623184350400_bib34","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1084\/jem.20052494","article-title":"Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy","volume":"203","author":"Reits","year":"2006","journal-title":"J Exp Med"},{"key":"2026030623184350400_bib35","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1667\/RR1860.1","article-title":"Up-regulation of the pro-inflammatory chemokine CXCL16 is a common response of tumor cells to ionizing radiation","volume":"173","author":"Matsumura","year":"2010","journal-title":"Radiat Res"},{"key":"2026030623184350400_bib36","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1158\/0008-5472.CAN-10-2820","article-title":"The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity","volume":"71","author":"Burnette","year":"2011","journal-title":"Cancer Res"},{"key":"2026030623184350400_bib37","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","article-title":"Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody","volume":"15","author":"Dewan","year":"2009","journal-title":"Clin Cancer Res"},{"key":"2026030623184350400_bib38","doi-asserted-by":"crossref","first-page":"e69527","DOI":"10.1371\/journal.pone.0069527","article-title":"The peripheral myeloid expansion driven by murine cancer progression is= reversed by radiation therapy of the tumor","volume":"8","author":"Crittenden","year":"2013","journal-title":"PLoS One"},{"key":"2026030623184350400_bib39","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/CJI.0b013e31828298e6","article-title":"Effects of tumor irradiation on host T-regulatory cells and systemic immunity in the context of adoptive T-cell therapy in mice","volume":"36","author":"Wei","year":"2013","journal-title":"J Immunother"},{"key":"2026030623184350400_bib40","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1007\/s00262-012-1307-4","article-title":"Chemotherapy broadens the range of tumor antigens seen by cytotoxic CD8(+) T cells in vivo","volume":"61","author":"Jackaman","year":"2012","journal-title":"Cancer Immunol Immunother"},{"key":"2026030623184350400_bib41","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1038\/mt.2010.159","article-title":"Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms","volume":"18","author":"Fridlender","year":"2010","journal-title":"Mol Ther"},{"key":"2026030623184350400_bib42","doi-asserted-by":"crossref","first-page":"798467","DOI":"10.1155\/2010\/798467","article-title":"Low-dose cyclophosphamide synergizes with dendritic cell-based immunotherapy in antitumor activity","volume":"2010","author":"Veltman","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"2026030623184350400_bib43","doi-asserted-by":"crossref","first-page":"e61895","DOI":"10.1371\/journal.pone.0061895","article-title":"Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity","volume":"8","author":"Lesterhuis","year":"2013","journal-title":"PLoS ONE"},{"key":"2026030623184350400_bib44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jtcvs.2003.08.034","article-title":"Immuno-gene therapy with interferon-beta before surgical debulking delays recurrence and improves survival in a murine model of malignant mesothelioma","volume":"127","author":"Kruklitis","year":"2004","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026030623184350400_bib45","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/sj.cgt.7700347","article-title":"The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor","volume":"8","author":"Mukherjee","year":"2001","journal-title":"Cancer Gene Ther"},{"key":"2026030623184350400_bib46","doi-asserted-by":"crossref","first-page":"7580","DOI":"10.1158\/0008-5472.CAN-05-0328","article-title":"Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy","volume":"65","author":"Broomfield","year":"2005","journal-title":"Cancer Res"},{"key":"2026030623184350400_bib47","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1158\/0008-5472.CAN-11-1782","article-title":"Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy","volume":"72","author":"Waitz","year":"2012","journal-title":"Cancer Res"},{"issue":"suppl","key":"2026030623184350400_bib48","doi-asserted-by":"crossref","first-page":"e17531","DOI":"10.1200\/jco.2010.28.15_suppl.e17531","article-title":"Cryoablation as an adjunctive therapy in a multimodality treatment program for malignant pleural mesothelioma [abstract]","author":"Cameron","year":"2010","journal-title":"J Clin Oncol"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/50\/5\/870\/67114489\/ajrcmb_50_5_870.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/50\/5\/870\/67114489\/ajrcmb_50_5_870.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:19:00Z","timestamp":1772857140000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/50\/5\/870\/8492535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,1]]},"published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2013-0472tr","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,5]]},"published":{"date-parts":[[2014,5,1]]}}}