Interleukin 21 impairs tumor immunosurveillance of colitis-associated colorectal cancer

Kesselring, Rebecca; Jauch, Dominik; Fichtner‐Feigl, Stefan

doi:10.4161/onci.19407

Cited by 14 publications

(16 citation statements)

References 8 publications

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“…Although both IL-17A and IL-17F are required for spontaneous CRC tumorigenesis [123, 125], in chemically induced colitis and in CAC tumorigenesis they play quite opposing roles [122, 126][124]. IL-17A deficient mice develop less CAC tumors of smaller size, underscoring the role of IL-17A in regulation of intestinal inflammation [127, 128], intratumoral inflammation [129, 130],, and tumor growth [122, 126, 130]. APC Min mice with established B. fragilis infection and chronic colitis exhibit lower tumor burden when IL-17A is neutralized [77].…”

Section: Inflammation As a Stimulator Of Cac Growth- Role Of Inflammamentioning

confidence: 99%

Inflammation and colorectal cancer: colitis-associated neoplasia

2012

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Connection between inflammation and cancer is a rapidly developing field. Epidemiological data suggests that inflammation along with distinct arms of host immune system plays a very important role in development and progression of many different cancers. Inflammatory bowel diseases (IBD) is an important risk factor for the development of colon cancer, namely colitis-associated cancer (CAC). The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and may differ between CAC and other forms of colorectal cancer. Recent work has shed light on the role of distinct immune cells, cytokines and other immune mediators in virtually all of the steps of colonic tumorigenesis, including tumor initiation and promotion as well as progression and metastasis. The close proximity of colonic tumors to the myriad of intestinal microbes, as well as instrumental role of microbiota in IBD, introduces microbes as new players capable of triggering inflammation and possibly promoting tumorigenesis. Various mechanisms of CAC tumorigenesis as well as new possible hints for the future approaches for prevention and therapy are discussed in this review.

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Section: Inflammation As a Stimulator Of Cac Growth- Role Of Inflammamentioning

confidence: 99%

Inflammation and colorectal cancer: colitis-associated neoplasia

2012

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“…As a promising cytokine for cancer immunotherapy, whilst IL-21 suppresses growth in certain tumors, including renal cell carcinoma and melanoma (9,14), it may promote growth in others, including colitis-associated colorectal cancer and follicular lymphoma (11,15). The function of IL-21 is complex, as it appears to have different functions in different tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have suggested that IL-21 is capable of suppressing growth in certain tumors, and it has already been used in phase I or II trials of patients with melanoma and renal cell carcinoma, with promising antitumor results obtained (9,10). However, IL-21 may also promote growth in certain other tumors, including colitis-associated colorectal cancer by impairing tumor immunosurveillance (11). Therefore, the function of IL-21 is extremely complex, as its use in different cancers has been shown to lead to different results (9–11).…”

Section: Introductionmentioning

confidence: 99%

“…However, IL-21 may also promote growth in certain other tumors, including colitis-associated colorectal cancer by impairing tumor immunosurveillance (11). Therefore, the function of IL-21 is extremely complex, as its use in different cancers has been shown to lead to different results (9–11). Further research is required to investigate this notable cytokine.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1–6 in mice

Wang

et al. 2016

Oncology Letters

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In the present study, adenovirus-mediated interleukin 21 (Ad5-IL-21-EGFP) gene expression was induced in Hepa1–6 cells to investigate whether IL-21 was capable of enhancing antitumor immunity and reducing tumorigenicity of Hepa1–6 in a mouse model. Mice were inoculated intradermally into the right flank with Hepa1–6 cells or Hepa1–6 cells infected with Ad5 or Ad5-IL-21. Four weeks later, the mice were sacrificed humanely, and the tumor volume, tumor weight and mouse spleen index were measured. The levels of IL-21, IL-4 and interferon (IFN)-γ levels in mouse serum and tumor tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Cell counting kit-8 (CCK-8) assay was used to detect the killing ability of spleen T cells and natural killer (NK) cells, and the proliferation ability of T cells. The expression of IL-21 was confirmed by reverse transcription-polymerase chain reaction, western blot analysis and ELISA assay in Ad5-IL-21-EGFP-infected Hepa1–6 cells. The overexpression of IL-21 significantly reduced the tumorigenicity of Hepa1–6 cells. The tumor volumes and tumor weights in Ad5-IL-21-Hepa1–6 mice were much smaller than those in the Ad5-Hepa1–6 group and Hepa1–6 wild-type group. The immunohistochemistry and ELISA assay demonstrated that IL-21 and IFN-γ levels were much higher while the IL-4 level was much lower in the Ad5-IL-21-Hepa1–6 group than in the other two groups. CCK-8 assay revealed that the killing ability of NK cells and T cells, and the proliferation ability of T cells in Ad5-IL-21-Hepa1–6 mice were higher than in the other two groups; the spleen index of Ad5-IL-21-Hepa1–6 mice was also higher than in the other groups. The data had a significant difference (P<0.01). In conclusion, IL-21 reduces tumorigenicity of Hepa1–6 by a mechanism involving enhanced activation of cell-mediated immunity in tumor-bearing mice.

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“…IL-21 was produced in excess in the gut of patients with UC-associated colon cancer [82]. This cytokine has a prominent function in tumor growth and immunosurveillance of colitis-associated tumorigenesis [83]. In mice with colitis-associated colon cancer (CAC) induced by azoxymethane (AOM) and dextran sulfate sodium (DSS), IL-21 was highly expressed in the intestines.…”

Section: Il-21 In Disorders Of Gastrointestinal Systemmentioning

confidence: 99%

IL-21 and Related Diseases

Niu¹,

Chen²

2011

J Clin Cell Immunol

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IL-21, which is produced by activated NKT cells and CD4 + T cells, exhibits pleiotropic effects not only on a variety of immune cells but also on non-immune cells. It has been demonstrated that IL-21 plays significant roles in the process of autoimmune diseases, inflammatory diseases and cancers. This review intends to give the reader an overview of this cytokine and the relationships between IL-21 and the related diseases of different body systems.

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Interleukin 21 impairs tumor immunosurveillance of colitis-associated colorectal cancer

Cited by 14 publications

References 8 publications

Inflammation and colorectal cancer: colitis-associated neoplasia

Inflammation and colorectal cancer: colitis-associated neoplasia

Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and reduces tumorigenicity of Hepa1–6 in mice

IL-21 and Related Diseases

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