Study of the Expression of Toll-Like Receptors in Different Histological Types of Colorectal Polyps and Their Relationship with Colorectal Cancer

Eiró, Noemí; González, Lucía; González, Luis O.; Andicoechea, Alejandro; Fernández-Díaz, María; Altadill, Antonio; Vizoso, F

doi:10.1007/s10875-012-9666-3

Cited by 38 publications

(45 citation statements)

References 28 publications

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“…Other contrasting studies, however, find that TLR9 expression is decreased in hyperplastic and villous polyps from patients who develop CRC, further supporting a possible protective role for TLR9 expression against malignant transformation in colorectal mucosa (134). To add to the complexity of the role of signaling components of IFN-I and gene products of IFN-I, a recent study reported that in vitro formation of colorectal tumor spheroids, in the absence of IFN-I treatment, induced transcription of ISGs via IRF9/STAT2 (135).…”

Section: Ifn-i In Colorectal Cancermentioning

confidence: 94%

The Protective Role of Type I Interferons in the Gastrointestinal Tract

2017

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The immune system of the gastrointestinal (GI) tract manages the significant task of recognizing and eliminating pathogens while maintaining tolerance of commensal bacteria. Dysregulation of this delicate balance can be detrimental, resulting in severe inflammation, intestinal injury, and cancer. Therefore, mechanisms to relay important signals regulating cell growth and immune reactivity must be in place to support GI homeostasis. Type I interferons (IFN-I) are a family of pleiotropic cytokines, which exert a wide range of biological effects including promotion of both pro- and anti-inflammatory activities. Using animal models of colitis, investigations into the regulation of intestinal epithelium inflammation highlight the role of IFN-I signaling during fine modulation of the immune system. The intestinal epithelium of the gut guides the immune system to differentiate between commensal and pathogenic microbiota, which relies on intimate links with the IFN-I signal-transduction pathway. The current paradigm depicts an IFN-I-induced antiproliferative state in the intestinal epithelium enabling cell differentiation, cell maturation, and proper intestinal barrier function, strongly supporting its role in maintaining baseline immune activity and clearance of damaged epithelia or pathogens. In this review, we will highlight the importance of IFN-I in intestinal homeostasis by discussing its function in inflammation, immunity, and cancer.

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Section: Ifn-i In Colorectal Cancermentioning

confidence: 94%

The Protective Role of Type I Interferons in the Gastrointestinal Tract

2017

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“…Therefore, while complex, there does appear to be a role of TLR-9 in the development of some tumors. For example, a study by Eiró et al found a potential protective role of TLR-9 expression against malignant transformation in the colorectal mucosa: TLR-9 expression was decreased in hyperplastic and villous polyps from patients who developed colorectal cancer (CRC) [45]. TLR-9 has also been shown to be associated with certain other tumors [26].…”

Section: Toll-like Receptor 9 (Tlr-9) Agonists In Tumor Immunotherapymentioning

confidence: 99%

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

Wittig¹,

Schmidt

Scheithauer³

et al. 2015

Critical Reviews in Oncology/Hematology

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The adaptive immune system has been the main focus of immunological strategies in oncology with only more recent approaches targeting innate immunity. Endosomal toll-like receptors (TLR-7, TLR-9) activate innate immune responses by signaling damage-associated molecular patterns (DAMP) from decaying tumor cells. This has led to the development of DNA-based TLR-9 agonists, which induce antitumor activity through innate and subsequent adaptive immune responses. Early clinical trials with CpG-ODN as TLR-9 agonists were associated with unfavorable tolerability and narrow clinical efficacy, leading to failure in pivotal trials. dSLIM, the active ingredient of MGN1703, is a DNA-based, radically different molecular alternative to CpG-ODN, which results in genuine antitumor immunomodulation. Preclinical and clinical studies of MGN1703 have confirmed that this TLR-9 agonist has therapeutic potential in a variety of solid tumors, while long-term treatment with high doses was very well tolerated. A pivotal trial of first-line maintenance treatment with MGN1703 in patients with metastatic colorectal cancer is underway.

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“…(Pimental-Nunes et al 2013). They may be a predictor of increased cancer risk in people with colon hyperplastic polyps (Eiro et al 2012). Increased expression of TLR4 in colon cancer (stroma) significantly accelerates the development of the disease and is a poor prognostic factor (Cammarota et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Expression of Toll-Like Receptors on Human Rectal Adenocarcinoma Cells

Tchórzewski

Lewkowicz

Dziki

et al. 2014

Arch. Immunol. Ther. Exp.

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The innate immune system uses Toll-like receptors (TLR) to detect the presence of pathogen patterns thus allowing for rapid host defense responses. Stimulation of TLR results in inflammatory response and regulatory cytokine production affecting acquired immunity. The aim of the study was an evaluation of TLR2 and TLR4 expression on the surface of human colon cancer cells in primary culture with or without autologous peripheral blood mononuclear cells. Surgical specimens of colon cancer were processed to obtain cancer cells. Cancer cells separation was conducted first by mechanical tissue disintegration and than by gradient centrifugation to obtain 95 % cell confluence. By staining the isolated cells the pathologist determined them as adenocarcinoma. Colon cancer cells were then co-cultured in 24 h culture alone or together with autologous lymphocytes. Reverse-transcription polymerase chain reaction was performed for detection of TLR2 and TLR4 mRNA in colon cancer and normal colon epithelial cells using commercially available primers. Resting as well as phytohemagglutinin or lipopolysaccharide (LPS) stimulated cells were tested. Receptor proteins on cancer cells were examined by immunohistochemistry. TLR4 mRNA was detected in cancer cells. Autologous lymphocytes do not exert any effect on these receptors expression. TLR4 mRNA expression was not observed in normal colon epithelial cells. TLR2 mRNA was present on LPS stimulated cancer cells as well as on resting and stimulated lymphocytes. Expression of TLR2 and TLR4 receptor proteins on colon cancer cells were confirmed by immunohistochemistry. TLR4 may be responsible for uncontrolled tumor growth under LPS stimulation in human colon environment.

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Study of the Expression of Toll-Like Receptors in Different Histological Types of Colorectal Polyps and Their Relationship with Colorectal Cancer

Cited by 38 publications

References 28 publications

The Protective Role of Type I Interferons in the Gastrointestinal Tract

The Protective Role of Type I Interferons in the Gastrointestinal Tract

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

Expression of Toll-Like Receptors on Human Rectal Adenocarcinoma Cells

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