CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood

Krijgsman, Daniëlle; Vries, Natasja L. de; Andersen, Morten Nørgaard; Skovbo, Anni; Tollenaar, Rob A.E.M.; Møller, Holger Jon; Hokland, Marianne; Kuppen, Peter J. K.

doi:10.3390/ijms21165925

Cited by 28 publications

(26 citation statements)

References 53 publications

(100 reference statements)

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“… 20 Soluble CD163 (sCD163) has also been associated with neoplastic and chronic inflammatory diseases. 21 All these recent results reinforce the notion that we are not being able to properly classify the response of monocytes to TLR agonists or in vivo infectious diseases; hence, it will be cumbersome to interpret circulating-monocyte behavior in other inflammatory pathologies.…”

Section: Introductionsupporting

confidence: 53%

In vitro Phenotype Induction of Circulating Monocytes: CD16 and CD163 Analysis

Karsulovic

Tempio

López

et al. 2021

JIR

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Introduction: CD14 (monocyte differentiation antigen, LPS binding protein -endotoxin receptor) and CD16 (FcγRIII, Low-affinity receptor for IgG) define three subpopulations of circulating monocytes with different inflammatory and phagocytic capabilities. Contradictory reports exist regarding both in vivo monocyte phenotype-disease association and response of these circulating monocytes to in vitro stimulation. We analyzed phenotypic changes in circulating monocytes when stimulated with LPS (pro-inflammatory stimulus) and IL-4 (alternative inflammatory stimulus). Methods: Mononuclear cells from nine healthy donors were extracted and studied for surface and intracellular markers using flow cytometry. PBMC were extracted using Ficoll technic and immediately analyzed using flow cytometry. Pro-inflammatory interleukin IL-1β and IL-6 were measured by intracellular cytometry. Mononuclear cells were stimulated using LPS and IL-4 as previously described. Changes against non-stimulated populations were statistically analyzed. Results: Compared to non-stimulated and IL-4 stimulated monocytes, LPS-stimulated cells display a singular pattern of markers, with higher levels of intracellular IL-1β and IL-6 directly correlating with CD14+CD163-cell frequency and diminishing membrane CD163 fluorescence. CD14+CD16-classical monocytes show greater percentage of CD163-cells upon LPS stimulation. CD86 levels on monocytes' surface did not change with LPS or IL-4 stimulation. Conclusions and Discussion: We showed that CD14+CD16-classical monocytes display higher sensitivity to LPS stimulation, with more IL-1β and IL-6 levels than intermediate and non-classical monocytes. This subset also diminishes its CD163 levels on the membrane after LPS stimulation with a contemporary raise in CD163-cells, suggesting that classical monocytes preferentially acquire CD163-defined M1 characteristics upon in vitro LPS stimulation. Intermediate and non-classical monocytes respond with lower levels of interleukins and display surface proteins in an M2-type profile (CD163+).

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Section: Introductionsupporting

confidence: 53%

In vitro Phenotype Induction of Circulating Monocytes: CD16 and CD163 Analysis

Karsulovic

Tempio

López

et al. 2021

JIR

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“…The speci c mechanism of action of M2 macrophages and Tregs in CRC, especially the molecular mechanism of interaction in local lymph nodes, will be the next focus of our group's research. In addition, studies have pointed out [37,38] that CD163 can be used as a potential prognostic biomarker for CRC patients, and Foxp3 can directly affect the prognosis of CRC patients. To further verify the impact of both on the monitoring and prognosis of CRC patients, our study analyzed the preoperative CEA, CA199 and CA724 levels in correlation with the number of M2 macrophages and Tregs.…”

Section: Discussionmentioning

confidence: 99%

A Study on the Correlation Between M2 Macrophages and Regulatory T Cells in the Progression of Colorectal Cancer

Chen

Gao

et al. 2022

Preprint

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Background: M2 macrophages and regulatory T cells (Tregs) can promote tumors and development by inhibiting the anti-tumor immune response. This study investigated the number of CD163‐positive M2 macrophages and Foxp3-positive Tregs in the progression of colorectal cancer. It also investigated the correlation and of M2 macrophages and Tregs.Methods: Postoperative tissue specimens and clinical data were collected from 197 patients with colorectal cancer who underwent initial surgical treatment in The Second Ward of Colorectal Surgery of the First Affiliated Hospital of Jinzhou Medical University from March 2020 to December 2020. Use immunohistochemical methods to detect the expression levels of CD163 protein-labeled M2 macrophages and Foxp3 protein-labeled Tregs in colorectal cancer tissues, matched paracancer tissues and lymph node tissues. Analyze the correlation between CD163 and Foxp3 in cancer tissues and lymph node tissues, as well as the relationship between clinicopathological characteristics and preoperative tumor markers. Results: M2 macrophages and Tregs were significantly positively correlated in cancer and lymph node tissues, which significantly increased in cancer and metastatic lymph node tissues. Interestingly, M2 macrophages in non-metastatic lymph nodes also increased significantly in patients with metastatic lymph nodes. Tregs stage I+II is higher than stage III+IV in paraneoplastic tissues. In addition, both CD163 and Foxp3 were upregulated with increasing tumor TNM stage, depth of infiltration, lymphatic metastasis, and depth of infiltration, and both were positively correlated with CEA. Conclusion: M2 macrophages and Tregs are important indicators of colorectal cancer progression and lymph node metastasis. There is a certain correlation between the two types of cells. It is possible that M2 macrophages, together with suppressor cells Tregs, promote an immunosuppressive environment.

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“…5 ). CD163 is a potential inflammation biomarker, which can be found either free (sCD163) or bound to the plasma membrane of macrophage cells 37 , and it is not known to be expressed in the normal colon tissue 38 . The CD163 protein tissue level can thus be a good indicator of the presence of active inflammatory foci.…”

Section: Discussionmentioning

confidence: 99%

Key biomarkers within the colorectal cancer related inflammatory microenvironment

Calu

Ionescu

Stanca

et al. 2021

Sci Rep

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Therapeutic approaches focused on the inflammatory microenvironment are currently gaining more support, as biomolecules involved in the inflammatory colorectal cancer (CRC) tumor microenvironment are being explored. We analyzed tumor and paired normal tissue samples from CRC patients (n = 22) whom underwent tumor resection surgery. We assessed 39 inflammation-involved biomolecules (multiplex magnetic bead-based immunoassay), CEA and CA19-9 (ELISA assay) and the tissue expression levels of occludin and also pErk, STAT1 and STAT3 transcriptional factors (western blot). Tumor staging has been established by histopathological evaluation of HE stained tumor tissue sections. We report 32 biomarkers displaying statistically significant differences in tumor vs. control. Additionally, positive statistical biomarker correlations were found between MMP2–IL8 and BAFF–IL8 (Pearson correlation coefficients > 0.751), while APRIL–MMP2, APRIL–BAFF and APRIL–IL8 were negatively correlated (correlation coefficients < − 0.650). While APRIL, BAFF, IL8 and MMP2 did not modulate with tumor stage, they were inversely related to the immune infiltrate level and CD163 tissue expression. We conclude that the significantly decreased APRIL and increased BAFF, IL8 and MMP2 expression were tumor-specific and deserve consideration in the development of new treatments. Also, the positive correlation between Chitinase 3-like 1 and IL8 (0.57) or MMP2 (0.50) suggest a role in tumor growth and metastasis pathways.

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CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood

Cited by 28 publications

References 53 publications

In vitro Phenotype Induction of Circulating Monocytes: CD16 and CD163 Analysis

In vitro Phenotype Induction of Circulating Monocytes: CD16 and CD163 Analysis

A Study on the Correlation Between M2 Macrophages and Regulatory T Cells in the Progression of Colorectal Cancer

Key biomarkers within the colorectal cancer related inflammatory microenvironment

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