ArticleOncotarget2015
Interleukin-21 sustains inflammatory signals that contribute to sporadic colon tumorigenesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Lentinula edodes cultured extract intake alleviates long-term immune deregulation induced by early-life gut microbiota dysbiosis.Scientific reports · 2025Article
- Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.Immunology and cell biology · 2025Article
- Rafoxanide negatively modulates STAT3 and NF-κB activity and inflammation-associated colon tumorigenesis.Cancer science · 2024Article
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Article
- Article
- Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy.Journal for immunotherapy of cancer · 2022Article
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- Review
- From inflammatory bowel disease to colorectal cancer: what's the role of miRNAs?Cancer cell international · 2022Review
- Data analytics and artificial intelligence in predicting length of stay, readmission, and mortality: a population-based study of surgical management of colorectal cancer.Discover oncology · 2022Article
- Article
- Programmed death-ligand 1 and mammalian target of rapamycin signaling pathway in locally advanced rectal cancer.Discover oncology · 2022Article
- Colitis-Associated Colorectal Cancer in Patients with Inflammatory Bowel Diseases in a Tertiary Referral Center: A Propensity Score Matching Analysis.Journal of clinical medicine · 2022Article
- Cushing syndrome and glucocorticoids: T-cell lymphopenia, apoptosis, and rescue by IL-21.The Journal of allergy and clinical immunology · 2022Article
- Complete mesocolic excision and central vascular ligation in colorectal cancer in the era of minimally invasive surgery.World journal of clinical cases · 2021Review
- Mesenteric closure with polymer-ligating clips after right colectomy with complete mesocolic excision for cancer and mesentery-based ileocolic resection for Crohn's disease.Techniques in coloproctology · 2021Article
- Central vascular ligation and mesentery based abdominal surgery.Discover oncology · 2021Review
- Role of 18F-PET-CT to predict pathological response after neoadjuvant treatment of rectal cancer.Discover oncology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin (IL)-21 triggers inflammatory signals that contribute to the growth of neoplastic cells in mouse models of colitis-associated colorectal cancer (CRC). Because most CRCs are sporadic and arise in the absence of overt inflammation we have investigated the role of IL-21 in these tumors in mouse and man. IL-21 was highly expressed in human sporadic CRC and produced mostly by IFN-γ-expressing T-bet/RORγt double-positive CD3+CD8- cells. Stimulation of human CRC cell lines with IL-21 did not directly activate the oncogenic transcription factors STAT3 and NF-kB and did not affect CRC cell proliferation and survival. In contrast, IL-21 modulated the production of protumorigenic factors by human tumor infiltrating T cells. IL-21 was upregulated in the neoplastic areas, as compared with non-tumor mucosa, of Apc(min/+) mice, and genetic ablation of IL-21 in such mice resulted in a marked decrease of both tumor incidence and size. IL-21 deficiency was associated with reduced STAT3/NF-kB activation in both immune cells and neoplastic cells, diminished synthesis of protumorigenic cytokines (that is, IL-17A, IL-22, TNF-α and IL-6), downregulation of COX-2/PGE2 pathway and decreased angiogenesis in the lesions of Apc(min/+) mice. Altogether, data suggest that IL-21 promotes a protumorigenic inflammatory circuit that ultimately sustains the development of sporadic CRC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.