The Immunological Landscape of M1 and M2 Macrophages and Their Spatial Distribution 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.authorLABERIANO-FERNANDEZ, Caddie
dc.contributor.authorBALDAVIRA, Camila Machado
dc.contributor.authorMACHADO-RUGOLO, Juliana
dc.contributor.authorTAMEGNON, Auriole
dc.contributor.authorPANDURENGAN, Renganayaki Krishna
dc.contributor.authorAB'SABER, Alexandre Muxfeldt
dc.contributor.authorBALANCIN, Marcelo Luiz
dc.contributor.authorTAKAGAKI, Teresa Yae
dc.contributor.authorNAGAI, Maria Aparecida
dc.contributor.authorCAPELOZZI, Vera Luiza
dc.contributor.authorPARRA, Edwin Roger
dc.date.accessioned2023-12-15T18:45:46Z
dc.date.available2023-12-15T18:45:46Z
dc.date.issued2023
dc.description.abstractSimple Summary Identifying biomarkers to guide immunotherapy regimens remains an unmet clinical need in malignant pleural mesothelioma. A potential source of such markers is tumor-associated macrophages (TAMs), which contribute to the immunosuppressive microenvironment of mesothelioma. By examining distinct subsets of pleural macrophages to identify their gene signatures and protein expression, we found that TAMs preferentially contribute to M2a and M2b phenotypes, and M2a, M2b, and M2c more specifically contributed to immune tolerance. CD206, ARG1, CD274, CD163, and MRP8-14 are potential therapeutic targets in this disease.Abstract Background: Several tumor-associated macrophages (TAMs) have shown promise as prognosticators in cancer. Our aim was to validate the importance of TAMs in malignant pleural mesothelioma (MPM) using a two-stage design. Methods: We explored The Cancer Genome Atlas (TCGA-MESO) to select immune-relevant macrophage genes in MPM, including M1/M2 markers, as a discovery cohort. This computational cohort was used to create a multiplex immunofluorescence panel. Moreover, a cohort of 68 samples of MPM in paraffin blocks was used to validate the macrophage phenotypes and the co-localization and spatial distribution of these immune cells within the TME and the stromal or tumor compartments. Results: The discovery cohort revealed six immune-relevant macrophage genes (CD68, CD86, CD163, CD206, ARG1, CD274), and complementary genes were differentially expressed by M1 and M2 phenotypes with distinct roles in the tumor microenvironment and were associated with the prognosis. In addition, immune-suppressed MPMs with increased enrichment of CD68, CD86, and CD163 genes and high densities of M2 macrophages expressing CD163 and CD206 proteins were associated with worse overall survival (OS). Interestingly, below-median distances from malignant cells to specific M2a and M2c macrophages were associated with worse OS, suggesting an M2 macrophage-driven suppressive component in these tumors. Conclusions: The interactions between TAMs in situ and, particularly, CD206+ macrophages are highly relevant to patient outcomes. High-resolution technology is important for identifying the roles of macrophage populations in tissue specimens and identifying potential therapeutic candidates in MPM.eng
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipWe acknowledge the Multiplex Immunofluorescence and Image Analysis Laboratory (MIIAL), part of the Translational Molecular Pathology Immunoprofiling Laboratory (TMP-IL) Moonshots Platform at the Department of Translational Molecular Pathology, The Universi
dc.description.sponsorshipMultiplex Immunofluorescence and Image Analysis Laboratory (MIIAL)
dc.description.sponsorshipResearch Medical Library at The University of Texas MD Anderson Cancer Center
dc.identifier.citationCANCERS, v.15, n.21, article ID 5116, 23p, 2023
dc.identifier.doi10.3390/cancers15215116
dc.identifier.eissn2072-6694
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/57382
dc.language.isoeng
dc.publisherMDPIeng
dc.relation.ispartofCancers
dc.rightsopenAccesseng
dc.rights.holderCopyright MDPIeng
dc.subjectmalignant pleural mesotheliomaeng
dc.subjecttranscriptomaeng
dc.subjectmultiplex immunofluorescenceeng
dc.subjectprognosiseng
dc.subjectin silico analysiseng
dc.subject.othertumor-associated macrophageseng
dc.subject.otherreceptor activatoreng
dc.subject.otherasbestoseng
dc.subject.otherchemotherapyeng
dc.subject.othercellseng
dc.subject.otherexpressioneng
dc.subject.othersurvivaleng
dc.subject.otherligandeng
dc.subject.wosOncologyeng
dc.titleThe Immunological Landscape of M1 and M2 Macrophages and Their Spatial Distribution in Patients with Malignant Pleural Mesotheliomaeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalLABERIANO-FERNANDEZ, Caddie:Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
hcfmusp.author.externalTAMEGNON, Auriole:Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
hcfmusp.author.externalPANDURENGAN, Renganayaki Krishna:Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
hcfmusp.author.externalPARRA, Edwin Roger:Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcCAMILA MACHADO BALDAVIRA
hcfmusp.contributor.author-fmusphcJULIANA MACHADO RUGOLO
hcfmusp.contributor.author-fmusphcALEXANDRE MUXFELDT AB'SABER
hcfmusp.contributor.author-fmusphcMARCELO LUIZ BALANCIN
hcfmusp.contributor.author-fmusphcTERESA YAE TAKAGAKI
hcfmusp.contributor.author-fmusphcMARIA APARECIDA NAGAI
hcfmusp.contributor.author-fmusphcVERA LUIZA CAPELOZZI
hcfmusp.description.articlenumber5116
hcfmusp.description.issue21
hcfmusp.description.volume15
hcfmusp.origemWOS
hcfmusp.origem.pubmed37958292
hcfmusp.origem.scopus2-s2.0-85176507814
hcfmusp.origem.wosWOS:001099490400001
hcfmusp.publisher.cityBASELeng
hcfmusp.publisher.countrySWITZERLANDeng
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