Dual association of serum interleukin-10 levels with colorectal cancer

Abtahi, Shabnam; Davani, Forogh; Mojtahedi, Zahra; Hosseini, Seyed Vahid; Bananzadeh, Alimohammad; Ghaderi, Abbas

doi:10.4103/0973-1482.199448

Cited by 37 publications

(20 citation statements)

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“…Local values of cytokines in liquid fraction of feces have shown predomination of anti-inflammatory cytokines TGF- β and IL-10 in patients with severe stadium of CRC (TNM stages III and IV, poor histological differentiation) as well as lower level of proinflammatory IL-1 β in patients with a more progressive disease (presence of metastasis in the liver, lung, and peritoneal carcinomatosis; Figures 1 , 2 , and 3 ). These results are in line with our and other previous studies claiming that serum levels of IL-10 and TGF- β were increased in patients with CRC in comparison to healthy controls and that CRC patients with worse prognosis had increased systemic concentration of IL-10 compared to patients with better prognosis [ 11 , 42 ].…”

Section: Discussionsupporting

confidence: 93%

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma

Jovanovic

Gajovic

Zdravković

et al. 2018

Mediators of Inflammation

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Background and Objectives The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Methods Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Results Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Conclusions Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

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Section: Discussionsupporting

confidence: 93%

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma

Jovanovic

Gajovic

Zdravković

et al. 2018

Mediators of Inflammation

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“…These observations are in line with studies showing elevated levels of these specific cytokines upon tumor progression. In humans, IL-10 serum levels increase over time during CRC progression, correlating with poor prognosis [ 39 , 40 , 41 , 42 ], while high levels of ARG-1 were associated with stage III–IV CRC tumors and lymph node metastasis [ 43 ]. Conversely, the protective roles of IL-12 and NOS2 have also been documented.…”

Section: Discussionmentioning

confidence: 99%

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

Karagiannidis

Vilet

Egal

et al. 2020

Cancers

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Tumor-associated macrophages (TAMs) in the gastrointestinal tumor microenvironment (TME) are known to polarize into populations exhibiting pro- or anti-tumoral activity in response to stimuli such as growth factors and cytokines. Our previous work has recognized granulocyte colony-stimulating factor (G-CSF) as a cytokine capable of influencing immune cells of the TME exhibiting pro-tumoral activity. Here, we aimed to focus on how G-CSF regulates TAM phenotype and function and the effects on gastrointestinal (GI) tumor progression. Thus, wildtype (WT) and G-CSFR−/− macrophages were examined for cytokine production, gene expression, and transcription factor activity. Adoptive transfer of WT or G-CSFR−/− macrophages into tumor-bearing mice was performed to study their influence in the progression of colon (MC38) and pancreatic (PK5L1940) tumor mouse models. Finally, the difference in cytotoxic potential between WT and G-CSFR−/− macrophages was examined both in vitro and in vivo. Our results indicate that G-CSF promotes increased IL-10 production and decreased IL-12 production, which was reversed in G-CSFR−/− macrophages for a pro-inflammatory phenotype. Furthermore, G-CSFR−/− macrophages were characterized by higher levels of NOS2 expression and NO production, which led to greater tumor related cytotoxicity both in vitro and in vivo. Our results suggest that in the absence of G-CSFR, macrophage-related tumor cytotoxicity was amplified. These findings, along with our previous reports, pinpoint G-CSF /G-CSFR as a prominent target for possible clinical applications that aim to control the TME and the GI tumor progression.

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“…Increased CXCL10 and IL-6 levels in patient blood have been associated with advanced CRC stage and IL-6 has been suggested as an independent adverse prognostic marker of survival [ 32 , 36 ]. Additionally, an increased pre-operative serum IL-10 level correlates with poor survival in CRC patients [ 37 , 38 ]. It has been reported that during intestinal inflammation macrophage produced IL-23 induce the production of the pro-inflammatory cytokines IL-6 and IL-17.…”

Section: Discussionmentioning

confidence: 99%

Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages

et al. 2018

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Abstract.BackgroundMacrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer. Accumulating evidence suggests that cancer-derived EVs are taken up by macrophages and modulate their phenotype and cytokine profile. However, the interactions of cancer-derived EVs with monocytes and macrophages at various differentiation and polarization states are poorly understood. In the current study, we have analyzed the uptake and functional effects of primary (SW480) and metastatic (SW620) isogenic colorectal cancer (CRC) cell line-derived EVs on monocytes (M), inactive macrophages (M0) and M1 and M2 polarized macrophages.MethodsTHP-1 monocytes were differentiated into M0 macrophages by addition of phorbol-12-myristate-13-acetate. Then M0 macrophages were further polarized into M1 and M2 macrophages in the presence of LPS, IFN- γ, IL-4, and IL-13 respectively. Internalization of SW480 and SW620-derived EVs was analyzed by flow cytometry and fluorescence microscopy. Changes in monocyte and macrophage immunophenotype and secretory profile upon EV exposure were analyzed by flow cytometry, quantitative PCR and Luminex assays.ResultsTHP-1 monocytes and M0 macrophages efficiently take up SW480 and SW620-derived EVs, and our results indicate that dynamin-dependent endocytic pathways may be implicated. Interestingly, SW480 and SW620-derived EVs increased CD14 expression in M0 macrophages whereas SW480-derived EVs decreased HLA-DR expression in M1 and M2 polarized macrophages. Moreover, SW480-derived EVs significantly increased CXCL10 expression in monocytes and M0 macrophages. In contrast, SW620-derived EVs induced secretion of IL-6, CXCL10, IL-23 and IL-10 in M0 macrophages. However, addition of CRC cell line-derived EVs together with LPS, IFN- γ (M1) and IL-4, IL-13 (M2) stimuli during macrophage polarization had no additional effect on cytokine expression in M1 and M2 macrophages.ConclusionOur results suggest that CRC cell line-derived EVs are internalized and reprogram the immunophenotype and secretory profile in monocytes and inactive macrophages inducing mixed M1 and M2 cytokine response. Although CRC EVs decreased HLA-DR expression in M1, M2 polarized macrophages, their effect on the secretory profile of M1 and M2 polarized macrophages was negligible.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0229-y) contains supplementary material, which is available to authorized users.

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Dual association of serum interleukin-10 levels with colorectal cancer

Abstract: Our results demonstrated a dual association of serum IL-10 levels in the initiation and progression of CRC. While lower IL-10 levels were associated with higher risk of the disease, its higher levels were associated with a poorer prognosis.

Cited by 37 publications

References 0 publications

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma

G-CSF and G-CSFR Induce a Pro-Tumorigenic Macrophage Phenotype to Promote Colon and Pancreas Tumor Growth

Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages

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