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: Maurizio Perdicchio, Lenneke A M Cornelissen, Ingeborg Streng-Ouwehand, Steef Engels, Marleen I Verstege, Louis Boon, Dirk Geerts, Yvette van Kooyk, Wendy W J Unger
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 8 Pg. 8771-82 (Feb 23 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26741508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polysaccharides
• RNA, Messenger
• N-Acetylneuraminic Acid

Topics

• Animals
• Apoptosis
• Blotting, Western
• Cell Adhesion
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Flow Cytometry
• Immunoenzyme Techniques
• Killer Cells, Natural (immunology)
• Melanoma, Experimental (immunology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• N-Acetylneuraminic Acid (metabolism)
• Polysaccharides (metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes, Regulatory (immunology)
• Tumor Cells, Cultured
• Tumor Microenvironment (immunology)