1. Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells
- Author
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Ingeborg Streng-Ouwehand, Louis Boon, Steef Engels, Dirk Geerts, Lenneke A. M. Cornelissen, Wendy W. J. Unger, Marleen I. Verstege, Yvette van Kooyk, Maurizio Perdicchio, Molecular cell biology and Immunology, CCA - Immuno-pathogenesis, CCA - Cancer biology and immunology, CCA - Cancer immunology, Other departments, and Pediatrics
- Subjects
0301 basic medicine ,Melanoma, Experimental ,Apoptosis ,T-Lymphocytes, Regulatory ,regulatory T cells ,Immunoenzyme Techniques ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Movement ,Tumor Cells, Cultured ,Tumor Microenvironment ,Medicine ,natural killer cells ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Cycle ,Cell cycle ,Flow Cytometry ,Killer Cells, Natural ,medicine.anatomical_structure ,Oncology ,sialic acid ,030220 oncology & carcinogenesis ,Research Paper ,tumor ,Regulatory T cell ,T cell ,Blotting, Western ,chemical and pharmacologic phenomena ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,Immune system ,Polysaccharides ,Cell Adhesion ,Animals ,RNA, Messenger ,Cell Proliferation ,Tumor microenvironment ,business.industry ,Cell growth ,immune regulation ,N-Acetylneuraminic Acid ,Sialic acid ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Immunology ,Cancer research ,business ,N-Acetylneuraminic acid - 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.
- Published
- 2016