ArticleGastroenterology2023
N-glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 62 citations in OpenAlex.
- Immune implications and therapeutic opportunities of tumor glycosylation.Nature cancer · 2026Review
- Abnormal glycosylation of MUC20 mediates TAM polarization and promotes immune escape in colorectal cancer.Communications biology · 2026Article
- Dietary palmitic acid inhibits colorectal cancer progression through enhancing bisecting GlcNAc.JCI insight · 2026Article
- Chemoresistance in the era of immunotherapy: challenges and novel combinatorial strategies for digestive system tumors.Frontiers in immunology · 2026Review
- Alterations in peripheral blood inflammatory mediators, vascular endothelial growth factor, and serum tumor markers in advanced non-small cell lung cancer patients treated with bevacizumab combined with chemotherapy.American journal of translational research · 2026Article
- Glycosylation-Related Gene Signature Identifies MFNG as a Key Driver of Proliferation and Metastasis in Colorectal Cancer.OncoTargets and therapy · 2026Article
- Cytokine and chemokine networks in colorectal cancer.Frontiers in immunology · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- ST6GAL1-mediated sialylation inhibits the antitumor immune response in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Integrin β6 expression in colorectal cancer cells promotes liver metastasis through enhanced adhesion to endothelial fibronectin.International journal of cancer · 2025Article
- Ginsenoside Rh2 in combination with IFNγ potentiated the anti-cancer effect by enhancing interferon signaling response in colorectal cancer cells.Acta pharmacologica Sinica · 2025Article
- Glycosylation in kidney diseases.Precision clinical medicine · 2025Review
- Prognostic and therapeutic implications related to glycosylation profiles of cancer-associated fibroblasts in colorectal cancer: insights from single-cell and bulk transcriptomics.Functional & integrative genomics · 2025Article
- Bisecting GlcNAc enhances CD8Experimental hematology & oncology · 2025Article
- Nordihydroguaiaretic acid inhibits bladder cancer metastasis through suppression of α1,3-mannosyltransferase expression and LRFN4 N-glycosylation.Journal of translational medicine · 2025Article
- Integrative multi-omics analysis reveals the LncRNA 60967.1-PLCD4-ATRA axis as a key regulator of colorectal cancer progression and immune response.Molecular cancer · 2025Article
- Glycoproteomics of Gastrointestinal Cancers and Its Use in Clinical Diagnostics.Journal of proteome research · 2025Review
- Deciphering the Metabolic Impact and Clinical Relevance of N-Glycosylation in Colorectal Cancer through Comprehensive Glycoproteomic Profiling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Downregulation of MGAT3 Promotes Benzo[ACS omega · 2025Article
- Abnormal proportions and functions of myeloid-derived suppressor cells in peripheral blood of patients with diffuse large B-cell lymphoma.BMC cancer · 2025Article
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsAdvanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored.
methodsSpontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines.
resultsThe conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor α (IFNγRα) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγRα expression was repressed in human CRC cells through changes in N-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling. Downregulation of the bisecting N-acetylglucosaminyltransferase III (MGAT3) expression was associated with IFN-γ resistance in all IFN-γ-resistant cells, and highly correlated with low IFNγRα expression in CRC tissues. Both ectopic and pharmacological reconstitution of MGAT3 expression with all-trans retinoic acid increased bisecting N-glycosylation, as well as IFNγRα protein stability and signaling.
conclusionsTogether, our results demonstrated that tumor-associated changes in N-glycosylation destabilize IFNγRα, causing IFN-γ resistance in CRC. IFN-γ sensitivity could be reestablished through the increase in MGAT3 expression, notably via all-trans retinoic acid treatment, providing new prospects for the treatment of immune-resistant CRC.
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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.