The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment.
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
19
06
2020
revised:
13
08
2020
accepted:
29
09
2020
pubmed:
8
10
2020
medline:
21
10
2021
entrez:
7
10
2020
Statut:
ppublish
Résumé
Macrophages are among the most common cells in the colorectal cancer microenvironment, but their prognostic significance is incompletely understood. Using multiplexed immunofluorescence for CD68, CD86, IRF5, MAF, MRC1 (CD206), and KRT (cytokeratins) combined with digital image analysis and machine learning, we assessed the polarization spectrum of tumor-associated macrophages in 931 colorectal carcinomas. We then applied Cox proportional hazards regression to assess prognostic survival associations of intraepithelial and stromal densities of M1-like and M2-like macrophages while controlling for potential confounders, including stage and microsatellite instability status. We found that high tumor stromal density of M2-like macrophages was associated with worse cancer-specific survival, whereas tumor stromal density of M1-like macrophages was not significantly associated with better cancer-specific survival. High M1:M2 density ratio in tumor stroma was associated with better cancer-specific survival. Overall macrophage densities in tumor intraepithelial or stromal regions were not prognostic. These findings suggested that macrophage polarization state, rather than their overall density, was associated with cancer-specific survival, with M1- and M2-like macrophage phenotypes exhibiting distinct prognostic roles. These results highlight the utility of a multimarker strategy to assess the macrophage polarization at single-cell resolution within the tumor microenvironment.
Identifiants
pubmed: 33023967
pii: 2326-6066.CIR-20-0527
doi: 10.1158/2326-6066.CIR-20-0527
pmc: PMC7785652
mid: NIHMS1635603
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8-19Subventions
Organisme : NCI NIH HHS
ID : R35 CA197735
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA118553
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA137178
Pays : United States
Organisme : NIDDK NIH HHS
ID : K24 DK098311
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169141
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA197879
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA167552
Pays : United States
Organisme : Cancer Research UK
ID : UK C10674/A27140
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R35 CA253185
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127003
Pays : United States
Organisme : NCI NIH HHS
ID : K07 CA190673
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA222940
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA230873
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA055075
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA151993
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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