The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment.

TitleThe Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment.
Publication TypeJournal Article
Year of Publication2021
AuthorsVäyrynen JP, Haruki K, Lau MChan, Väyrynen SA, Zhong R, Costa ADias, Borowsky J, Zhao M, Fujiyoshi K, Arima K, Twombly TS, Kishikawa J, Gu S, Aminmozaffari S, Shi S, Baba Y, Akimoto N, Ugai T, da Silva A, Guerriero JL, Song M, Wu K, Chan AT, Nishihara R, Fuchs CS, Meyerhardt JA, Giannakis M, Ogino S, Nowak JA
JournalCancer Immunol Res
Volume9
Issue1
Pagination8-19
Date Published2021 01
ISSN2326-6074
KeywordsAged, Colorectal Neoplasms, Female, Humans, Macrophage Activation, Male, Microsatellite Instability, Middle Aged, Phenotype, Prognosis, Proportional Hazards Models, Prospective Studies, Tumor Microenvironment, Tumor-Associated Macrophages, United States
Abstract

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.

DOI10.1158/2326-6066.CIR-20-0527
Alternate JournalCancer Immunol Res
PubMed ID33023967
PubMed Central IDPMC7785652
Grant ListR35 CA197735 / CA / NCI NIH HHS / United States
R01 CA118553 / CA / NCI NIH HHS / United States
U01 CA167552 / CA / NCI NIH HHS / United States
R01 CA137178 / CA / NCI NIH HHS / United States
K24 DK098311 / DK / NIDDK NIH HHS / United States
UM1 CA186107 / CA / NCI NIH HHS / United States
R01 CA169141 / CA / NCI NIH HHS / United States
R03 CA197879 / CA / NCI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
K07 CA190673 / CA / NCI NIH HHS / United States
R21 CA222940 / CA / NCI NIH HHS / United States
R21 CA230873 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
R01 CA151993 / CA / NCI NIH HHS / United States
UK C10674/A27140 / CRUK_ / Cancer Research UK / United Kingdom
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