ArticleJournal for immunotherapy of cancer2023
Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Advances in deciphering intratumoral versus peritumoral heterogeneity of infiltrating lymphocytes in pancreatic cancer: a spatial perspective.Translational oncology · 2026Review
- Single-Cell Glycomics of the Pancreatic Tumor Microenvironment: Technologies, Glyco-Immune Checkpoints, and Tumor-Immune Communication.Advanced biology · 2026Review
- Immune implications and therapeutic opportunities of tumor glycosylation.Nature cancer · 2026Review
- Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site.European journal of immunology · 2026Article
- Sialic acids modulate immune responses in cancer: Therapeutic opportunities.The Journal of biological chemistry · 2026Review
- Writers and readers of sialylation in immunoregulation in cancer.The Journal of biological chemistry · 2026Review
- Sweet Surprises: Decoding Tumor-Associated Glycosylation in Cancer Progression and Therapeutic Potential.Cells · 2026Review
- Overcoming resistance to anti-PD-1/PD-L1 therapy in cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Machine Learning-Based Sialylation-Associated Gene Signature Predicts Prognosis and Immune Landscape in Hepatocellular Carcinoma: Validation via Multi-Omics Analysis and in vitro Assays.Journal of hepatocellular carcinoma · 2026Article
- IL-6 as a central driver of immune evasion in PDAC: from IDO-mediated tolerance to multi-pathway immunosuppression.Frontiers in immunology · 2026Review
- Integration of transcriptome and Mendelian randomization analyses in exploring the extracellular vesicle-related biomarkers of diabetic kidney disease.Renal failure · 2025Article
- Ganglioside therapy in cancer molecular insights and therapeutic opportunities.Discover oncology · 2025Review
- Tumor desialylation surpasses anti-PD-L1 checkpoint therapy in restoring anti-tumor immunity in a murine model for colorectal cancer.International journal of cancer · 2025Article
- Analytical dissection of minor glycoforms and glycoprotein associations in rAAV preparations by multimodal glycoproteomics.Analytical and bioanalytical chemistry · 2025Article
- Stromal fibrin shapes immune infiltration landscape of pancreatic ductal adenocarcinoma.Biomaterials · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment.European journal of immunology · 2025Review
- Four-gene Prognostic Signature and Risk of Brain Metastasis of Lung Adenocarcinoma.Molecular carcinogenesis · 2025Article
- IL-4-STAT6-induced high Siglec-G/10 expression aggravates the severe immune suppressive tumor microenvironment and impedes the efficacy of immunotherapy in head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Targeting Mesothelin Enhances Personalized Neoantigen Vaccine Induced Antitumor Immune Response in Orthotopic Pancreatic Cancer Mouse Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC.
methodIn this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40.
resultThe absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4
conclusionOur results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.
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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.