Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/106955
Title: | The Two Faces of Tumor-Associated Macrophages and Their Clinical Significance in Colorectal Cancer | Authors: | Pinto, Marta L. Rios, Elisabete Durães, Cecília Ribeiro, Ricardo Machado, José C. Mantovani, Alberto Barbosa, Mario A. Carneiro, Fátima Oliveira, Maria J. |
Keywords: | colorectal cancer; tumor immunomodulation; tumor-associated macrophages; human macrophage surface markers; macrophage polarization; prognostic and tumor relapse | Issue Date: | 2019 | Publisher: | Frontiers Media S.A. | Project: | POCI- 01-0145-FEDER-031859 PD/BD/81103/2011 SFRH/BPD/99442/2014 FCT grant - IF/01066/2012 |
Serial title, monograph or event: | Frontiers in Immunology | Volume: | 10 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/106955 | ISSN: | 1664-3224 | DOI: | 10.3389/fimmu.2019.01875 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer.pdf | 4.35 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
138
checked on Aug 19, 2024
WEB OF SCIENCETM
Citations
133
checked on Aug 2, 2024
Page view(s)
70
checked on Aug 27, 2024
Download(s)
30
checked on Aug 27, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License