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The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer

dc.contributor.authorPinto, Marta L.
dc.contributor.authorRios, Elisabete
dc.contributor.authorDurães, Cecília
dc.contributor.authorRibeiro, Ricardo
dc.contributor.authorMachado, José C.
dc.contributor.authorMantovani, Alberto
dc.contributor.authorBarbosa, Mário A.
dc.contributor.authorCarneiro, Fatima
dc.contributor.authorOliveira, Maria J.
dc.date.accessioned2019-09-30T16:39:11Z
dc.date.available2019-09-30T16:39:11Z
dc.date.issued2019
dc.description© 2019 Pinto, Rios, Durães, Ribeiro, Machado, Mantovani, Barbosa, Carneiro and Oliveira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractMacrophages are one of the immune populations frequently found in colorectal tumors and high macrophage infiltration has been associated with both better and worst prognosis. Importantly, according to microenvironment stimuli, macrophages may adopt different polarization profiles, specifically the pro-inflammatory or M1 and the anti-inflammatory or M2, which display distinct functions. Therefore, concomitantly with the number of tumor-associated macrophages (TAMs), their characterization is fundamental to unravel their relevance in cancer. Here, we profiled macrophages in a series of 150 colorectal cancer (CRC) cases by immunohistochemistry, using CD68 as a macrophage lineage marker, CD80 as a marker of pro-inflammatory macrophages, and CD163 as a marker of anti-inflammatory macrophages. Quantifications were performed by computer-assisted analysis in the intratumoral region, tumor invasive front, and matched tumor adjacent normal mucosa (ANM). Macrophages, specifically the CD163+ ones, were predominantly found at the tumor invasive front, whereas CD80+ macrophages were almost exclusively located in the ANM, which suggests a predominant anti-inflammatory polarization of TAMs. Stratification according to tumor stage revealed that macrophages, specifically the CD163+ ones, are more prevalent in stage II tumors, whereas CD80+ macrophages are predominant in less invasive T1 tumors. Specifically in stage III tumors, higher CD68, and lower CD80/CD163 ratio associated with decreased overall survival. Importantly, despite the low infiltration of CD80+ cells in colorectal tumors, multivariate logistic regression revealed a protective role of these cells regarding the risk for relapse. Overall, this work supports the involvement of distinct microenvironments, present at the intra-tumor, invasive front and ANM regions, on macrophage modulation, and uncovers their prognostic value, further supporting the relevance of including macrophage profiling in clinical settings.pt_PT
dc.description.sponsorshipThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project MAGICIAM: a MAcrophaGe Immunomodulatory-delivery system to prevent Cancer Invasion and Metastasis (POCI-01-0145-FEDER-031859). FCT further supported this work under MP PhD grant (PD/BD/81103/2011), CD post-doctoral grant (SFRH/BPD/99442/2014), and MO FCT Investigator grant (IF/01066/2012).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront. Immunol. 10:1875pt_PT
dc.identifier.doi10.3389/fimmu.2019.01875
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/10451/39661
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationPOCI-01-0145-FEDER-031859pt_PT
dc.relationPD/BD/81103/2011pt_PT
dc.relationGenetic profile and clonal evolution of stomach premalignant conditions: detecting the point of no return in gastric carcinogenesis
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectColorectal cancerpt_PT
dc.subjectTumor immunomodulationpt_PT
dc.subjectTumor-associated macrophagespt_PT
dc.subjectHuman macrophage surface markerspt_PT
dc.subjectMacrophage polarizationpt_PT
dc.subjectPrognostic and tumor relapsept_PT
dc.titleThe two faces of tumor-associated macrophages and their clinical significance in colorectal cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BPD/99442/2014
oaire.awardTitleGenetic profile and clonal evolution of stomach premalignant conditions: detecting the point of no return in gastric carcinogenesis
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F99442%2F2014/PT
oaire.citation.startPage1875pt_PT
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume10pt_PT
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication81ac9527-0d0d-4cc1-89e1-0ff54e28f3b3
relation.isProjectOfPublication.latestForDiscovery81ac9527-0d0d-4cc1-89e1-0ff54e28f3b3

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