Stromal cell sialylation suppresses T cells in inflammatory tumour microenvironments: A new tumour stromal cell immune checkpoint?
Stromal cell sialylation suppresses T cells in inflammatory tumour microenvironments: A new tumour stromal cell immune checkpoint?
Abstract Immunosuppressive tumour microenvironments (TME) reduce the effectiveness of immune responses in cancer. Non-haematopoietic mesenchymal stromal cells (MSC), the precursor to cancer associated fibroblasts (CAFs), dictate tumour progression by enhancing immune cell suppression. Hyper-sialylation of glycans promotes immune evasion in cancer, but the role of sialyation in stromal cell-mediated immunosuppression is unknown. Here we study changes in sialyltransferase (ST) enzymes and associated surface expressed sialic acid in stromal cells following inflammatory and tumour secretome conditioning. We show that tumour conditioned stromal cells have increased levels of sialyltransferases, α2,3/6 linked sialic acid and siglec ligands. In tumour models of solid (colorectal cancer) and haematological (multiple myeloma) stromal rich tumours, stromal cell sialylation is associated with enhanced immunosuppression. Using datasets and patient samples, we confirm that targeting sialylation in tumour stromal cells reverses immune cell exhaustion. Targeting stromal cell sialylation may represent a novel immune checkpoint to reactivate anti-tumour immunity.
Kerr Emma、Hogan Aisling M、O?ˉMalley Grace、Hynes Sean、Egan Hannah、Treacy Oliver、De Veirman Kim、Craughwell Michael、Ritter Thomas、Leonard Niamh A、Lynch Kevin、Sheehan Margaret、Canney Aoife、Vanderkerken Karin、Dunne Philip D、Redmond Keara、Ryan Aideen E、Egan Laurence J、O?ˉDwyer Michael E
Patrick G Johnston Centre for Cancer Research, Queen?ˉs University BelfastLambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Department of Colorectal surgery, Galway University HospitalDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDivision of Anatomical Pathology, Galway University Hospital,||Discipline of Pathology, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDepartment of Haematology and Immunology (HEIM), Vrije Universiteit BrusselDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health SciencesRegenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||C¨2RAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland GalwayDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayDivision of Anatomical Pathology, Galway University Hospital,Division of Anatomical Pathology, Galway University Hospital,Department of Haematology and Immunology (HEIM), Vrije Universiteit BrusselPatrick G Johnston Centre for Cancer Research, Queen?ˉs University BelfastPatrick G Johnston Centre for Cancer Research, Queen?ˉs University BelfastDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Regenerative Medicine Institute (REMEDI), College of Medicine Nursing and Health Sciences||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||C¨2RAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland GalwayDiscipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway||Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland GalwayBlood Cancer Network of Ireland (BCNI)||Department of Hematology, Galway University Hospital and School of Medicine
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Kerr Emma,Hogan Aisling M,O?ˉMalley Grace,Hynes Sean,Egan Hannah,Treacy Oliver,De Veirman Kim,Craughwell Michael,Ritter Thomas,Leonard Niamh A,Lynch Kevin,Sheehan Margaret,Canney Aoife,Vanderkerken Karin,Dunne Philip D,Redmond Keara,Ryan Aideen E,Egan Laurence J,O?ˉDwyer Michael E.Stromal cell sialylation suppresses T cells in inflammatory tumour microenvironments: A new tumour stromal cell immune checkpoint?[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2021.06.18.447879.点此复制
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