Contribution of IL-33 to the Pathogenesis of Colorectal Cancer

Cui, Guanglin; Yuan, Ang; Pang, Zhigang; Zheng, Wei; Li, Zhenfeng; Goll, Rasmus

doi:10.3389/fonc.2018.00561

Cited by 30 publications

(22 citation statements)

References 90 publications

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“…Previous studies confirmed important role of IL-33 in CRC pathogenesis 13,14 . It is known that IL-33 activates core stem cell genes, recruits macrophages into the cancer microenvironment and stimulates them to produce prostaglandin E2, which all promote carcinogenesis of CRC and metastasis of cancers 16,30 .…”

Section: Figure 4 Discussionsupporting

confidence: 56%

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Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

et al. 2021

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Background/Aim. Reactive thrombocytosis, as a paraneoplastic syndrome, is often observed in cancer patients. A variety of tumor-related humoral factors and cytokines contribute to tumor-stimulated thrombopoiesis. However, the exact role of these cytokines in the pathogenesis of thrombocytosis remains unclear. The aim of this study was to analyze systemic values of cytokines and clinical-pathological characteristics in colorectal carcinoma (CRC) patients with and without thrombocytosis. Methods. In this study, 59 CRC patients were involved and divided in two groups according to the number of platelets. We recorded and analyzed the data about: age, gender, size of the cancer, localization, metastasis, vascular or lymph vessel invasion, nuclear grade, histological differentiation rate, TNM stage and concentration of cytokines (IL-1, IL-33, IL-12, IL-17 and IFN-γ) in both groups. Results. CRC patients with thrombocytosis had significantly higher nuclear grade of colorectal cancer (p=0.002); higher percentage of detectable metastatic lesions in liver (p=0.002), lung (p=0.001), peritoneal carcinomatosis (p=0.001), detectable invasion of blood (p=0.012) and lymph vessels (p=0.010), respectively. Concentrations of tumor markers AFP, CEA and CA 19-9 and serum values of IL-1 and IL-33 were significantly higher in CRC patients with thrombocytosis. IL-1/IL-12 (p=0.016), IL-1/IFN-γ (p=0.007), IL-1/IL-17 (p=0.006), IL-33/IL-12 (p=0.001), IL-33/IFN-γ (p=0.001), IL-33/IL-17 (p=0.002), and IL-33/IL-1 (p=0.006) ratios were significantly higher in CRC patients with thrombocytosis in comparison to CRC patients without thrombocytosis. Analysis of Receiver Operating Characteristic (ROC) curves showed that IL-1 (AUC=0.718; 95% Cl: 0.567-0.868); sensitivity 69,2%, specificity 62,9% and IL-33 (AUC=0.763; 95% Cl: 0.614-0.911); sensitivity 84,6%, specificity 65,7%, can serve as possible markers for paraneoplastic thrombocytosis in CRC patients. Conclusion. IL-1 and IL-33 are significantly correlated to high thrombocyte number in patients with more aggressive CRC.

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Section: Figure 4 Discussionsupporting

confidence: 56%

“…Interleukin (IL)-33, an IL-1 family member, plays an essential role in the regulation of immune response after cellular stress or damage 13,14 . Recent study revealed that IL-33 by biding to its receptor ST2 inhibits host anti-tumor immunity, remodels tumor stroma and enhances angiogenesis, thereby promoting the development of CRC 15 .…”

Section: Introductionmentioning

confidence: 99%

Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

et al. 2021

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“…Finally, host anti-tumor immunity is regulated by a complex immune cellular network in patents with CRC (1,3,70,(91)(92)(93). For instance, a number of recent studies have reported that diverse TH subsets TH9, TH17 and TH22 and their main cytokines such as IL-9, IL-17 and IL-22 participate in the modulation of immune response in patients with CRC (91).…”

Section: The Possible Mechanisms Leading To a Distinct Therapeutic Efmentioning

confidence: 99%

“…Unfortunately, metastasis is often observed at the time of diagnosis, and curative surgical resection becomes impossible in these patients. Thus, to improve the prognosis of metastatic CRC (mCRC) patients, many researchers have investigated the escape immunosurveillance mechanisms by which the CRC progresses and metastases persistently (1)(2)(3)(4). A growing body of evidence from various studies has demonstrated that immune checkpoints are negative regulators for host anti-tumor immune function and could significantly suppress the host anti-tumor immune reactivity (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses

Cui

2021

Front. Oncol.

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Current clinical studies showed distinct therapeutic outcomes, in which CRC patients with mismatch repair-deficient (dMMR)/microsatellite instability high (MSI-H) seem to be relatively more “sensitive” in response to anti-programmed death-1 receptor (PD-1)/programmed death-1 receptor ligand 1 (PD-L1) therapy than those with mismatch repair-proficient (pMMR)/microsatellite instability-low (MSI-L). The mechanisms by which the same PD-1/PD-L1 blockades lead to two distinct therapeutic responses in CRC patients with different MSI statuses remain poorly understood and become a topic of great interest in both basic research and clinical practice. In this review of the potential mechanisms for the distinct response to PD-1/PD-L1 blockades between dMMR/MSI-H CRCs and pMMR/MSI-L CRCs, relevant references were electronically searched and collected from databases PubMed, MEDLINE, and Google scholar. Sixty-eight articles with full text and 10 articles by reference-cross search were included for final analysis after eligibility selection according to the guidelines of PRISMA. Analysis revealed that multiple factors e.g. tumor mutation burden, immune cell densities and types in the tumor microenvironment, expression levels of PD-1/PD-L1 and cytokines are potential determinants of such distinct response to PD-1/PD-L1 blockades in CRC patients with different MSI statuses which might help clinicians to select candidates for anti-PD-1/PD-L1 therapy and improve therapeutic response in patients with CRC.

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“…Although controversial, evidence points out an important role of the alarmin IL-33 in intestinal tumorigenesis [ 114 ]. IL-33 is elevated in CRC, both in tissue and serum samples, and the IL-33/ST2L axis shapes immune cell populations in the tumor, promoting the accumulation or depletion of immunosuppressive and anti-tumorigenic cells, respectively [ 115 , 116 ]. Moreover, the IL-33/ST2L axis is critical for Treg expansion and, therefore, it could indirectly promote tumor suppression.…”

Section: Type 2 Immunity Responses In the Context Of Colorectal Camentioning

confidence: 99%

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

Gámez‐Belmonte

Erkert

Wirtz

et al. 2020

IJMS

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The gut is among the most complex organs of the human body. It has to exert several functions including food and water absorption while setting up an efficient barrier to the outside world. Dysfunction of the gut can be life-threatening. Diseases of the gastrointestinal tract such as inflammatory bowel disease, infections, or colorectal cancer, therefore, pose substantial challenges to clinical care. The intestinal epithelium plays an important role in intestinal disease development. It not only establishes an important barrier against the gut lumen but also constantly signals information about the gut lumen and its composition to immune cells in the bowel wall. Such signaling across the epithelial barrier also occurs in the other direction. Intestinal epithelial cells respond to cytokines and other mediators of immune cells in the lamina propria and shape the microbial community within the gut by producing various antimicrobial peptides. Thus, the epithelium can be considered as an interpreter between the microbiota and the mucosal immune system, safeguarding and moderating communication to the benefit of the host. Type 2 immune responses play important roles in immune-epithelial communication. They contribute to gut tissue homeostasis and protect the host against infections with helminths. However, they are also involved in pathogenic pathways in inflammatory bowel disease and colorectal cancer. The current review provides an overview of current concepts regarding type 2 immune responses in intestinal physiology and pathophysiology.

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Contribution of IL-33 to the Pathogenesis of Colorectal Cancer

Cited by 30 publications

References 90 publications

Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

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