ArticleCancer immunology research2023
β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- γδ T cells in colorectal and liver cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- γδ T cells and cancer.The Journal of clinical investigation · 2026Review
- Why in vivo models of disease remain indispensable.Disease models & mechanisms · 2026Article
- Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis.Science immunology · 2026Article
- Mechanisms of immune resistance in microsatellite-stable colorectal cancer.Frontiers in oncology · 2026Review
- Immunotherapy Resistance in dMMR/MSI-H Colorectal Cancer: Unraveling Mechanisms and Exploring Overcoming Strategies.Journal of immunology research · 2026Review
- Functional heterogeneity of γδ T cells in colorectal cancer.Frontiers in immunology · 2026Review
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- Rational Design and Organoid-Based Evaluation of a Cocktail CAR-γδ T Cell Therapy for Heterogeneous Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dysregulation of γδ intraepithelial lymphocytes precedes Crohn's disease-like ileitis.Science immunology · 2025Article
- Uncovering the mysteries of human gamma delta T cells: from origins to novel therapeutics.Frontiers in immunology · 2025Review
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.eLife · 2024Article
- Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.bioRxiv : the preprint server for biology · 2024Article
- Article
- Anoikis-related CTNND1 is associated with immuno-suppressive tumor microenvironment and predicts unfavorable immunotherapeutic outcome in non-small cell lung cancer.Journal of Cancer · 2024Article
- A Ménage à trois: NLRC5, immunity, and metabolism.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
32 authors at 12 institutions in 5 countries.
Funding
Abstract
Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs. In contrast with healthy intestinal or colonic tissue, we found that γδIELs were largely absent from the microenvironment of both mouse and human tumors, and that butyrophilin-like (BTNL) molecules, which can critically regulate γδIEL through direct γδTCR interactions, were also downregulated in tumors. We then demonstrated that β-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased γδIEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of β-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant β-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and γδ T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts γδIEL immunosurveillance and furthers cancer progression.
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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.