title: Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells.
abstract: The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created "sialic acid low" tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing "sialic acid low" tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Perdicchio
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lenneke A M
authors.initials: LA
authors.lastname: Cornelissen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Streng-Ouwehand
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Steef
authors.initials: S
authors.lastname: Engels
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marleen I
authors.initials: MI
authors.lastname: Verstege
authors.affiliation: EPIRUS Biopharmaceuticals, Leiden, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pediatrics, Division of Infectious Diseases, ErasmusMC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: Unger
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D011134:Polysaccharides; D012333:RNA, Messenger; D019158:N-Acetylneuraminic Acid
keywords: immune regulation; natural killer cells; regulatory T cells; sialic acid; tumor