{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:23:59Z","timestamp":1770294239862,"version":"3.49.0"},"reference-count":90,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IRCCS Policlinico San Mattteo","award":["#08050"],"award-info":[{"award-number":["#08050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.<\/jats:p>","DOI":"10.3390\/ijms22169014","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:47:52Z","timestamp":1629668872000},"page":"9014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7436-8401","authenticated-orcid":false,"given":"Daniela","family":"Lisini","sequence":"first","affiliation":[{"name":"Cell Therapy Production Unit-UPTC and Cerebrovascular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Lettieri","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-8255","authenticated-orcid":false,"given":"Sara","family":"Nava","sequence":"additional","affiliation":[{"name":"Cell Therapy Production Unit-UPTC and Cerebrovascular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Accordino","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Frigerio","sequence":"additional","affiliation":[{"name":"Cell Therapy Production Unit-UPTC and Cerebrovascular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-9309","authenticated-orcid":false,"given":"Chandra","family":"Bortolotto","sequence":"additional","affiliation":[{"name":"Unit of Radiology, Department of Intensive Medicine, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-7725","authenticated-orcid":false,"given":"Andrea","family":"Lancia","sequence":"additional","affiliation":[{"name":"Unit of Radiation Therapy, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-7869","authenticated-orcid":false,"given":"Andrea Riccardo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Unit of Radiation Therapy, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-1230","authenticated-orcid":false,"given":"Francesco","family":"Agustoni","sequence":"additional","affiliation":[{"name":"Unit of Oncology, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pandolfi","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-4229","authenticated-orcid":false,"given":"Davide","family":"Piloni","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Comoli","sequence":"additional","affiliation":[{"name":"Cell Factory and Pediatric Hematology-Oncology Unit, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-4694","authenticated-orcid":false,"given":"Angelo Guido","family":"Corsico","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0929-4394","authenticated-orcid":false,"given":"Giulia Maria","family":"Stella","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Diseases, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1053\/sonc.2002.30237","article-title":"The epidemiology of mesothelioma","volume":"29","author":"Britton","year":"2002","journal-title":"Semin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abbott, D.M., Bortolotto, C., Benvenuti, S., Lancia, A., Filippi, A.R., and Stella, G.M. (2020). Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge. Cancers, 12.","DOI":"10.3390\/cancers12051186"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1900953","DOI":"10.1183\/13993003.00953-2019","article-title":"ERS\/ESTS\/EACTS\/ESTRO guidelines for the management of malignant pleural mesothelioma","volume":"55","author":"Scherpereel","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1200\/JCO.2006.09.7634","article-title":"Phase II study of erlotinib in patients with malignant pleural mesothelioma: A Southwest Oncology Group Study","volume":"25","author":"Garland","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1158\/1078-0432.CCR-04-1940","article-title":"Cancer and Leukemia Group B (CALGB 30101). Gefitinib in patients with malignant mesothelioma: A phase II study by the Cancer and Leukemia Group B","volume":"11","author":"Govindan","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1593\/neo.101156","article-title":"Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma","volume":"13","author":"Ou","year":"2011","journal-title":"Neoplasia"},{"key":"ref_7","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":"Transl. Lung Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Terenziani, R., Zoppi, S., Fumarola, C., Alfieri, R., and Bonelli, M. (2021). Immunotherapeutic Approaches in Malignant Pleural Mesothelioma. Cancers, 13.","DOI":"10.3390\/cancers13112793"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1470-2045(18)30765-4","article-title":"Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): A multicentre, open-label, randomised, non-comparative, phase 2 trial","volume":"20","author":"Scherpereel","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S1470-2045(17)30446-1","article-title":"Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): A multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial","volume":"18","author":"Maio","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_11","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_12","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_13","doi-asserted-by":"crossref","unstructured":"Lorenzini, E., Ciarrocchi, A., and Torricelli, F. (2021). Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations. J. Clin. Med., 10.","DOI":"10.3390\/jcm10112470"},{"key":"ref_14","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_15","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_16","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_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1116\/1.3582324","article-title":"Carbon nanotubes and pleural damage: Perspectives of nanosafety in the light of asbestos experience","volume":"6","author":"Stella","year":"2011","journal-title":"Biointerphases"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41416-019-0661-9","article-title":"Metabolic rewiring and redox alterations in malignant pleural mesothelioma","volume":"122","author":"Urso","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.21037\/tlcr-20-673","article-title":"Immunotherapy in malignant pleural mesothelioma: A review of literature data","volume":"6","author":"Menis","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Tolani, B., Acevedo, L.A., Hoang, N.T., and He, B. (2018). Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010238"},{"key":"ref_22","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_23","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_24","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_25","doi-asserted-by":"crossref","unstructured":"de Perrot, M. (2021). Prognostic role of PD-L1 in malignant pleural mesothelioma: Unraveling the complexity of the tumor microenvironment in mesothelioma. Ann. Thorac. Surg., 21.","DOI":"10.1016\/j.athoracsur.2020.12.052"},{"key":"ref_26","first-page":"1157","article-title":"Role of evaluating tumor infiltrating lymphocytes, programmed death 1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma","volume":"55","author":"Losi","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.pathol.2020.09.018","article-title":"Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status","volume":"53","author":"Rrapaj","year":"2021","journal-title":"Pathology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1261241","DOI":"10.1080\/2162402X.2016.1261241","article-title":"Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma","volume":"6","author":"Marcq","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, M.C., Hwang, S.H., Kim, N.Y., Lee, H.S., Ji, S., Yang, Y., and Kim, Y. (2018). Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4720-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1084\/jem.20100587","article-title":"HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment","volume":"207","author":"Corzo","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ceresoli, G., Bombardieri, E., and D\u2019Incalci, M. (2019). Microenvironment and Immunology of the Human Pleural Malignant Mesothelioma. Mesothelioma, Springer.","DOI":"10.1007\/978-3-030-16884-1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1677\/erc.1.00766","article-title":"Identification and validation of cell surface antigens for antibody targeting in oncology","volume":"11","author":"Carter","year":"2004","journal-title":"Endocr Relat. Cancer."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1089\/dna.2005.24.271","article-title":"Receptor-targeted cancer therapy","volume":"24","author":"Richter","year":"2005","journal-title":"DNA Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.coph.2008.08.011","article-title":"Antibody-based identification of cell surface antigens: Targets for cancer therapy","volume":"8","author":"Loo","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: From T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S1535-6108(03)00276-9","article-title":"Advancing the field of drug delivery: Taking aim at cancer","volume":"4","author":"Moses","year":"2003","journal-title":"Cancer Cell."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"999","DOI":"10.2217\/imt-2018-0002","article-title":"An overview of cancer immunotherapeutic strategies","volume":"10","author":"Wahid","year":"2018","journal-title":"Immunotherapy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.3389\/fmicb.2019.02924","article-title":"Trained Immunity for Personalized Cancer Immunotherapy: Current Knowledge and Future Opportunities","volume":"10","author":"Paraschoudi","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1038\/s41467-020-17670-y","article-title":"A decade of immune-checkpoint inhibitors in cancer therapy","volume":"11","author":"Robert","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1007\/s10147-019-01548-1","article-title":"Combination therapy with PD-1 or PD-L1 inhibitors for cancer","volume":"25","author":"Hayashi","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/JTO.0b013e318191520c","article-title":"Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma","volume":"4","author":"Ramalingam","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1158\/0008-5472.CAN-21-0340","article-title":"Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors","volume":"81","author":"Wang","year":"2021","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.21873\/cgp.20183","article-title":"Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome","volume":"17","author":"Lacerenza","year":"2020","journal-title":"Cancer Genom. Proteomics."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ebiom.2017.09.025","article-title":"MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of Cancers of Unknown Primary Origin","volume":"24","author":"Stella","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s10555-020-09900-y","article-title":"Tumor-stroma biomechanical crosstalk: A perspective on the role of caveolin-1 in tumor progression","volume":"39","author":"Lolo","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e04796","DOI":"10.7554\/eLife.04796","article-title":"Reproducibility Project: Cancer Biology. Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis","volume":"4","author":"Fiering","year":"2015","journal-title":"elife"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1148\/radiol.2015151169","article-title":"Radiomics: Images Are More Than Pictures, They Are Data","volume":"278","author":"Gillies","year":"2016","journal-title":"Radiology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s41747-018-0068-z","article-title":"Radiomics: The Facts and the Challenges of Image Analysis","volume":"2","author":"Rizzo","year":"2018","journal-title":"Eur. Radiol. Exp."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/S1470-2045(18)30413-3","article-title":"A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: An imaging biomarker, retrospective multicohort study","volume":"19","author":"Sun","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Martini, K., and Frauenfelder, T. (2021). Old Borders and New Horizons in Multimodality Imaging of Malignant Pleural Mesothelioma. Thorac. Cardiovasc. Surg.","DOI":"10.1055\/s-0041-1728714"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.lungcan.2016.09.003","article-title":"Imaging in pleural mesothelioma: A review of the 13th International Conference of the International Mesothelioma Interest Group","volume":"101","author":"Armato","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.rcl.2018.01.005","article-title":"Update of MR Imaging for Evaluation of Lung Cancer","volume":"56","author":"Ciliberto","year":"2018","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zheng, J., Gong, X.Q., Tao, Y.Y., Wang, R., Yang, G., Li, J.D., Ren, T., Li, Z.M., Yang, C., and Wang, W.C. (2021). Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma. Front. Oncol.","DOI":"10.3389\/fonc.2020.594366"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Meyer, H.J., Wienke, A., and Surov, A. (2019). Association Between VEGF Expression and Diffusion Weighted Imaging in Several Tumors-A Systematic Review and Meta-Analysis. Diagnostics, 9.","DOI":"10.3390\/diagnostics9040126"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2147\/OTT.S36915","article-title":"Pegylated liposomal doxorubicin in malignant pleural mesothelioma: A possible guardian for long-term survival","volume":"5","author":"Zarogoulidis","year":"2012","journal-title":"Oncol. Targets Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1097\/JTO.0b013e31818b174d","article-title":"Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: A phase II study","volume":"3","author":"Hillerdal","year":"2008","journal-title":"J. Thorac. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jconrel.2015.10.019","article-title":"Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed","volume":"220 Pt A","author":"Ando","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejps.2015.09.015","article-title":"Encapsulation in a rapid-release liposomal formulation enhances the anti-tumor efficacy of pemetrexed in a murine solid mesothelioma-xenograft model","volume":"81","author":"Eldin","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1002\/jps.20163","article-title":"Avidin\/biotin-liposome system injected in the pleural space for drug delivery to mediastinal lymph nodes","volume":"93","author":"Medina","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.2147\/IJN.S202568","article-title":"Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection","volume":"14","author":"Marazioti","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2147\/IJN.S186344","article-title":"Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: An in vitro study","volume":"14","author":"Cova","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1016\/j.athoracsur.2011.04.106","article-title":"Paclitaxel-loaded expansile nanoparticles in a multimodal treatment model of malignant mesothelioma","volume":"92","author":"Schulz","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/rcr2.145","article-title":"Repetitive responses to nanoparticle albumin-bound paclitaxel and carboplatin in malignant pleural mesothelioma","volume":"4","author":"Kanai","year":"2016","journal-title":"Respirol. Case Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3218","DOI":"10.1016\/j.xphs.2019.06.012","article-title":"Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate","volume":"108","author":"Sakurai","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_66","first-page":"3","article-title":"Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human melanoma","volume":"9","author":"Oble","year":"2009","journal-title":"Cancer Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1093\/annonc\/mdz398","article-title":"Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: A systematic review and meta-analysis","volume":"30","author":"Dafni","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"118486","DOI":"10.1016\/j.lfs.2020.118486","article-title":"Expression and clinical significance of CXC chemokines in the glioblastoma microenvironment","volume":"261","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.3389\/fimmu.2017.01594","article-title":"Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma","volume":"8","author":"Hargadon","year":"2017","journal-title":"Front Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1473-0502(02)00041-1","article-title":"Dendritic cells in vaccination therapies of malignant diseases","volume":"27","author":"Brossart","year":"2002","journal-title":"Transfus Apher Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s40425-019-0719-5","article-title":"Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8+ T cells","volume":"7","author":"Wang","year":"2019","journal-title":"J. Immunother Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3389\/fonc.2020.00777","article-title":"Cellular Immunotherapy and Locoregional Administration of CAR T-Cells in Malignant Pleural Mesothelioma","volume":"10","author":"Belderbos","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.3389\/fimmu.2018.02759","article-title":"Combination Strategies to Optimize Efficacy of Dendritic Cell-Based Immunotherapy","volume":"9","author":"Dammeijer","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e1328341","DOI":"10.1080\/2162402X.2017.1328341","article-title":"Trial watch: Dendritic cell-based anticancer immunotherapy","volume":"6","author":"Garg","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Dumoulin, D.W., Cornelissen, R., Bezemer, K., Baart, S.J., and Aerts, J.G.J.V. (2021). Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I\/II Trials. Vaccines, 9.","DOI":"10.3390\/vaccines9050525"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.lungcan.2021.05.004","article-title":"CAR T-cell therapy for pleural mesothelioma: Rationale, preclinical development, and clinical trials","volume":"157","author":"Chintala","year":"2021","journal-title":"Lung Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1080\/14712598.2021.1843628","article-title":"Mesothelin-targeted CAR-T cell therapy for solid tumors","volume":"21","author":"Klampatsa","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gray, S.G. (2021). Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01513-7"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13287-019-1331-9","article-title":"The effect of culture media on large-scale expansion and characteristic of adipose tissue-derived mesenchymal stromal cells","volume":"10","author":"Czapla","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ejmech.2017.07.063","article-title":"Malignant Pleural Mesothelioma: State of the art and advanced cell therapy","volume":"142","author":"Facchetti","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Petrella, F., Rimoldi, I., Rizzo, S., and Spaggiari, L. (2017). Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery. Medicines, 4.","DOI":"10.3390\/medicines4040087"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5893981","DOI":"10.1155\/2021\/5893981","article-title":"Circulating Exosomal miR-96 as a Novel Biomarker for Radioresistant Non-Small-Cell Lung Cancer","volume":"2021","author":"Zheng","year":"2021","journal-title":"J. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13287-021-02265-1","article-title":"Mesenchymal stem\/stromal cells as a valuable source for the treatment of immune-mediated disorders","volume":"12","author":"Markov","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Burgio, S., Noori, L., Marino Gammazza, A., Campanella, C., Logozzi, M., Fais, S., Bucchieri, F., Cappello, F., and Caruso Bavisotto, C. (2020). Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155432"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Cocc\u00e8, V., Franz\u00e8, S., Brini, A.T., Giann\u00ec, A.B., Pascucci, L., Ciusani, E., Alessandri, G., Farronato, G., Cavicchini, L., and Sordi, V. (2019). In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020061"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jconrel.2017.07.023","article-title":"Mesenchymal stem\/stromal cell extracellular vesicles: From active principle to next generation drug delivery system","volume":"262","author":"Crivelli","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_87","first-page":"316","article-title":"Hydrogel scaffolds for tissue engineering: Progress and challenges","volume":"2013","author":"Yacoub","year":"2013","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Siemionow, M.Z., and Eisenmann-Klein, M. (2010). Tissue Engineering. Plastic and Reconstructive Surgery, Springer.","DOI":"10.1007\/978-1-84882-513-0"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4","DOI":"10.13172\/2052-9643-1-1-607","article-title":"Cancer tissue engineering\u2014New perspectives in understanding the biology of solid tumours\u2014A critical review","volume":"1","author":"Ricci","year":"2013","journal-title":"OA Tissue Eng."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.scib.2020.04.012","article-title":"Biomaterial scaffold-based local drug delivery systems for cancer immunotherapy","volume":"65","author":"Yang","year":"2020","journal-title":"Sci. Bull."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/9014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:48:29Z","timestamp":1760165309000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/9014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,20]]},"references-count":90,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22169014"],"URL":"https:\/\/doi.org\/10.3390\/ijms22169014","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,20]]}}}