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

Bibliographic Details
Main Author: Pinto, Marta L.
Publication Date: 2019
Other Authors: Rios, Elisabete, Durães, Cecília, Ribeiro, Ricardo, Machado, José C., Mantovani, Alberto, Barbosa, Mário A., Carneiro, Fatima, Oliveira, Maria J.
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/39661
Summary: © 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.
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spelling The two faces of tumor-associated macrophages and their clinical significance in colorectal cancerColorectal cancerTumor immunomodulationTumor-associated macrophagesHuman macrophage surface markersMacrophage polarizationPrognostic and tumor relapse© 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.Macrophages 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.This 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).FrontiersRepositório da Universidade de LisboaPinto, Marta L.Rios, ElisabeteDurães, CecíliaRibeiro, RicardoMachado, José C.Mantovani, AlbertoBarbosa, Mário A.Carneiro, FatimaOliveira, Maria J.2019-09-30T16:39:11Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/39661engFront. Immunol. 10:18751664-322410.3389/fimmu.2019.01875info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:11:32Zoai:repositorio.ulisboa.pt:10451/39661Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:04:58.891189Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
title The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
spellingShingle The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
Pinto, Marta L.
Colorectal cancer
Tumor immunomodulation
Tumor-associated macrophages
Human macrophage surface markers
Macrophage polarization
Prognostic and tumor relapse
title_short The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
title_full The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
title_fullStr The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
title_full_unstemmed The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
title_sort The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer
author Pinto, Marta L.
author_facet Pinto, Marta L.
Rios, Elisabete
Durães, Cecília
Ribeiro, Ricardo
Machado, José C.
Mantovani, Alberto
Barbosa, Mário A.
Carneiro, Fatima
Oliveira, Maria J.
author_role author
author2 Rios, Elisabete
Durães, Cecília
Ribeiro, Ricardo
Machado, José C.
Mantovani, Alberto
Barbosa, Mário A.
Carneiro, Fatima
Oliveira, Maria J.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pinto, Marta L.
Rios, Elisabete
Durães, Cecília
Ribeiro, Ricardo
Machado, José C.
Mantovani, Alberto
Barbosa, Mário A.
Carneiro, Fatima
Oliveira, Maria J.
dc.subject.por.fl_str_mv Colorectal cancer
Tumor immunomodulation
Tumor-associated macrophages
Human macrophage surface markers
Macrophage polarization
Prognostic and tumor relapse
topic Colorectal cancer
Tumor immunomodulation
Tumor-associated macrophages
Human macrophage surface markers
Macrophage polarization
Prognostic and tumor relapse
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.
publishDate 2019
dc.date.none.fl_str_mv 2019-09-30T16:39:11Z
2019
2019-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/39661
url http://hdl.handle.net/10451/39661
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Front. Immunol. 10:1875
1664-3224
10.3389/fimmu.2019.01875
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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