Role of IL-17A in the Development of Colitis-Associated Cancer

Hyun, Yil Sik; Han, Dong Soo; Lee, A Reum; Eun, Chang Soo; Yu, Yeon Hwa; Jeong, Jae Yoon; Park, Hye Sun; Bae, Jeong Hun; Youn, Jee Hee

doi:10.1016/s0016-5085(11)60224-2

Cited by 26 publications

(35 citation statements)

References 25 publications

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“…Given that infiltration of IL-17 + immune cells negatively influences the prognosis of colon cancer in humans and promotes tumor growth in mouse models [4][5][6][7]25 , we determined the concentration of IL-17 in Itch −/− mice treated with DSS and AOM. We detected significantly higher concentrations of IL-17A in the serum of Itch −/− mice than in that of Itch +/+ mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We found that the ubiquitin ligase Itch was essential for the inhibition of IL-17, which is a major pro-inflammatory factor in colitis and colon cancer [4][5][6][7]25,30 . Our results showed that by targeting ROR-γt for ubiquitination, Itch prevented chronic IL-17 expression in the colonic mucosa.…”

Section: Discussionmentioning

confidence: 96%

“…These cytokines in turn promote IL-17 expression and the adaptive response 32 . A pro-tumorigenic role for dysregulated IL-17 expression has been well documented in colon cancer and other solid cancers [4][5][6][7]25 . In patients with stage I-II colon cancer, a signature of high IL-17 expression is associated with rapid progression to lethal metastatic disease and therefore serves as a strong indicator of poor clinical outcome 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence suggests a crucial role for IL-17 in colon inflammation and carcinogenesis [4][5][6][7] . Local producers of IL-17 in the gut include the T H 17 subset of CD4 + T cells 8 , γδ T cells 7 and innate lymphoid cells (ILCs) 9 .…”

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confidence: 99%

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Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination

et al. 2016

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Dysregulated expression of interleukin 17 (IL-17) in the colonic mucosa is associated with colonic inflammation and cancer. However, the cell-intrinsic molecular mechanisms by which IL-17 expression is regulated remain unclear. We found that deficiency in the ubiquitin ligase Itch led to spontaneous colitis and increased susceptibility to colon cancer. Itch deficiency in the TH17 subset of helper T cells, innate lymphoid cells and γδ T cells resulted in the production of elevated amounts of IL-17 in the colonic mucosa. Mechanistically, Itch bound to the transcription factor ROR-γt and targeted ROR-γt for ubiquitination. Inhibition or genetic inactivation of ROR-γt attenuated IL-17 expression and reduced spontaneous colonic inflammation in Itch(-/-) mice. Thus, we have identified a previously unknown role for Itch in regulating IL-17-mediated colonic inflammation and carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination

et al. 2016

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“…Neutralization of IL-17A with a specific antibody prevented the ETBFinduced acceleration of colorectal tumor development (Wu et al, 2009). IL-17A is also important for the development of CAC induced by administration of the procarcinogen AOM and the irritant DSS (Hyun et al, 2012;Tanaka et al, 2003;Tong et al, 2012). Although IL-17A and IL-17F belong to the same family and signal through the same receptors and effector mechanisms, IL-17F plays a role opposite to IL-17A and protects mice from CAC induction (Tong et al, 2012).…”

Section: Il-23 and Il-17 Axis Of Inflammationmentioning

confidence: 99%

Tumor-Elicited Inflammation and Colorectal Cancer

Wang

Karin

2015

Advances in Cancer Research

150

113

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Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

Bhat

Nisar

Singh

et al. 2022

Cancer Communications

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Colorectal cancer (CRC) is a predominant life‐threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer‐associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix‐remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell‐like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine‐ and chemokine‐mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine‐ and chemokine‐mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

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Role of IL-17A in the Development of Colitis-Associated Cancer

Cited by 26 publications

References 25 publications

Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination

Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-γt ubiquitination

Tumor-Elicited Inflammation and Colorectal Cancer

Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

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