Abstract
ObjectiveMonocytes and macrophages can infiltrate into tumor microenvironment and regulate the progression of tumors. This study aimed at determining the frequency of different subsets of circulating monocytes and tumor infiltrating macrophages (TIMs) in patients with colorectal cancer (CRC).MethodsThe frequency of different subsets of circulating monocytes was characterized in 46 CRC patients and 22 healthy controls (HC) by flow cytometry. The frequency of different subsets of macrophages was analyzed in TIMs from 30 tumor tissues and in lamina propria mononuclear cells (LPMCs) from 12 non-tumor tissues. The concentrations of plasma cytokines and carcinoembryonic antigen (CEA) were determined. The potential association of these measures with the values of clinical parameters was analyzed.ResultsIn comparison with that in the HC, the percentages of circulating CD14+CD169+, CD14+CD169+CD163+ and CD14+CD169+CD206+ monocytes and TIMs CD14+CD169+ as well as IL-10+CD14+CD169+, but not IL-12+ CD14+CD169+ macrophages were significantly increased, accompanied by higher levels of plasma IL-10 in the CRC patients. The percentages of CD14+CD169+ circulating monocytes and TIM macrophages were associated with the stage of disease and correlated positively with the levels of plasma IL-10 and CEA in CRC patients.ConclusionOur data suggest that an increase in the frequency of CD14+CD169+ cells may be associated with the development and progression of CRC and is concomitant rise of both, pro-tumor (M2-like, IL-10 producing) and anti-tumor (M1-like, IL-12 producing) monocytes and infiltrating macrophages. The frequency of CD14+CD169+ circulating monocytes and infiltrating macrophages may serve as a biomarker for evaluating the pathogenic degrees of CRC.
Highlights
Colorectal cancer (CRC) is one of the most prevalent malignant tumors with a high mortality
The percentages of CD14+CD169+ circulating monocytes and tumor infiltrating macrophages (TIMs) macrophages were associated with the stage of disease and correlated positively with the levels of plasma IL-10 and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients
Our data suggest that an increase in the frequency of CD14+CD169+ cells may be associated with the development and progression of CRC and is concomitant rise of both, pro-tumor
Summary
Colorectal cancer (CRC) is one of the most prevalent malignant tumors with a high mortality. Macrophages can be classically activated into M1 cells that express inducible nitric oxidase (iNOS), IL-12 and high levels of costimulator molecules while resident tissue macrophages and tumor-associated macrophages are likely to express CD163, 206, arginase and IL-10, a M2 phenotype [12,13,14,15,16,17]. Macrophages, like their parental monocytes, express CD14, a co-receptor of TLR4, which has been commonly used for identifying macrophages and monocytes from intestinal mucosa and peripheral blood [18, 19]. The frequency of circulating CD169+ monocytes and tumor infiltrating macrophages in the CRC and their potential association with the progression of CRC have not been clarified
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