Glioblastomas exploit truncated O - linked glycans for local and distant immune modulation via the macrophage galactose-type lectin.

Autor:	Dusoswa SA; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Verhoeff J; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Abels E; Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129.; Department of Radiology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129., Méndez-Huergo SP; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina., Croci DO; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.; Laboratorio de Inmunopatología, Instituto de Histología y Embriología de Mendoza, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, C5500 Mendoza, Argentina., Kuijper LH; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., de Miguel E; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Wouters VMCJ; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Best MG; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.; Department of Pathology, Cancer Center Amsterdam and Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Rodriguez E; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Cornelissen LAM; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., van Vliet SJ; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Wesseling P; Department of Pathology, Cancer Center Amsterdam and Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Breakefield XO; Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129.; Department of Radiology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129., Noske DP; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Würdinger T; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.; Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129.; Department of Radiology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129., Broekman MLD; Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129.; Department of Radiology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, MA 02129.; Department of Neurosurgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.; Department of Neurosurgery, Haaglanden Medical Center, 2512 VA The Hague, The Netherlands., Rabinovich GA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina; gabyrabi@gmail.com jj.garciavallejo@amsterdamumc.nl.; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina., van Kooyk Y; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands., Garcia-Vallejo JJ; Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands; gabyrabi@gmail.com jj.garciavallejo@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Feb 18; Vol. 117 (7), pp. 3693-3703. Date of Electronic Publication: 2020 Feb 04.
DOI:	10.1073/pnas.1907921117
Abstrakt:	Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163 + TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1 + TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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