ArticleScience translational medicine2012
Expression of RORγt marks a pathogenic regulatory T cell subset in human colon cancer.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 203 citations in OpenAlex.
- Association of tumor-infiltrating lymphocytes with survival depends on primary tumor sidedness in stage III colon cancers (NCCTG N0147) [Alliance].Annals of oncology : official journal of the European Society for Medical Oncology · 2022Trial
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- Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis.The Journal of clinical investigation · 2015Trial
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- Ulcerative colitis and colorectal cancer: Pathogenic insights and precision strategies for prevention and treatment.World journal of gastrointestinal oncology · 2025Review
- Differential Effects of High-Fiber and Low-Fiber Diets on Antitumor Immunity and Colon Tumor Progression in a Murine Model.Cancer prevention research (Philadelphia, Pa.) · 2025Article
- Unveiling the link between chronic inflammation and cancer.Metabolism open · 2025Review
- Revisiting Tregs in cancer and beyond: immunological control and therapeutic potential.Frontiers in immunology · 2025Review
- Jianpi Lishi Jiedu Decoction (JLJD) Inhibit Th17 Cell Differentiation via the Jak/Stat3/RORγt Pathway in Colorectal Adenomas.Journal of inflammation research · 2025Article
- Th17 cell function in cancers: immunosuppressive agents or anti-tumor allies?Cancer cell international · 2024Review
- Multiplex imaging of localized prostate tumors reveals altered spatial organization of AR-positive cells in the microenvironment.iScience · 2024Article
- Multi-omics and single cell characterization of cancer immunosenescence landscape.Scientific data · 2024Article
- Regulatory T Cell Dysfunction in Autoimmune Diseases.International journal of molecular sciences · 2024Review
- Advances in molecular mechanisms of inflammatory bowel disease‑associated colorectal cancer (Review).Oncology letters · 2024Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 3 institutions in 2 countries.
Funding
Abstract
The role of regulatory T cells (T(regs)) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, T(regs) have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different T(reg) subsets. We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt. T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt. Surprisingly, loss of IL-17A had a dual effect: IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer. Thus, we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.
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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.