Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorQUALIOTTO, Aline Nery
dc.contributor.authorBALDAVIRA, Camila Machado
dc.contributor.authorBALANCIN, Marcelo
dc.contributor.authorAB'SABER, Alexandre
dc.contributor.authorTAKAGAKI, Teresa
dc.contributor.authorCAPELOZZI, Vera Luiza
dc.date.accessioned2023-12-15T18:56:25Z
dc.date.available2023-12-15T18:56:25Z
dc.date.issued2023
dc.description.abstractBackgroundThe combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.MethodsThe discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.ResultsMost patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15-10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09-6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58-9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.ConclusionTumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipThe author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Sao Paulo Research Foundation (FAPESP
dc.description.sponsorship2018/20403-6
dc.description.sponsorship2022/06510-0
dc.description.sponsorship2023/02755-0), the National Council for Sci [2018/20403-6, 2022/06510-0, 2023/02755-0]
dc.description.sponsorshipSao Paulo Research Foundation [303735/2021-0]
dc.description.sponsorshipNational Council for Scientific and Technological Development (CNPq) [001]
dc.description.sponsorshipCoordenao de Aperfeioamento de Pessoal de Nvel Superior - Brasil
dc.identifier.citationFRONTIERS IN IMMUNOLOGY, v.14, article ID 1268927, 17p, 2023
dc.identifier.doi10.3389/fimmu.2023.1268927
dc.identifier.issn1664-3224
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/57526
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Immunology
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectmalignant mesotheliomaeng
dc.subjectmesothelineng
dc.subjectPD-L1eng
dc.subjectimmune cellseng
dc.subjectcomputational quantificationeng
dc.subjectimmunohistochemistryeng
dc.subject.otherphase-ieng
dc.subject.othercellseng
dc.subject.otherimmunotoxineng
dc.subject.otherovarianeng
dc.subject.otherchemotherapyeng
dc.subject.otherdiagnosiseng
dc.subject.otherresponseseng
dc.subject.otherinfusioneng
dc.subject.otherupdateeng
dc.subject.wosImmunologyeng
dc.titleMesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesotheliomaeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcALINE NERY QUALIOTTO
hcfmusp.contributor.author-fmusphcCAMILA MACHADO BALDAVIRA
hcfmusp.contributor.author-fmusphcMARCELO LUIZ BALANCIN
hcfmusp.contributor.author-fmusphcALEXANDRE MUXFELDT AB'SABER
hcfmusp.contributor.author-fmusphcTERESA YAE TAKAGAKI
hcfmusp.contributor.author-fmusphcVERA LUIZA CAPELOZZI
hcfmusp.description.articlenumber1268927
hcfmusp.description.volume14
hcfmusp.origemWOS
hcfmusp.origem.pubmed37901248
hcfmusp.origem.scopus2-s2.0-85174899554
hcfmusp.origem.wosWOS:001087437900001
hcfmusp.publisher.cityLAUSANNEeng
hcfmusp.publisher.countrySWITZERLANDeng
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