TY - JOUR
T1 - Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells
AU - Perdicchio, Maurizio
AU - Cornelissen, Lenneke A M
AU - Streng-Ouwehand, Ingeborg
AU - Engels, Steef
AU - Verstege, Marleen I
AU - Boon, Louis
AU - Geerts, Dirk
AU - van Kooyk, Yvette
AU - Unger, Wendy W J
PY - 2016/2/23
Y1 - 2016/2/23
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis
KW - Blotting, Western
KW - Cell Adhesion
KW - Cell Cycle
KW - Cell Movement
KW - Cell Proliferation
KW - Flow Cytometry
KW - Immunoenzyme Techniques
KW - Killer Cells, Natural/immunology
KW - Melanoma, Experimental/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - N-Acetylneuraminic Acid/metabolism
KW - Polysaccharides/metabolism
KW - RNA, Messenger/genetics
KW - Real-Time Polymerase Chain Reaction
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - T-Lymphocytes, Regulatory/immunology
KW - Tumor Cells, Cultured
KW - Tumor Microenvironment/immunology
U2 - 10.18632/oncotarget.6822
DO - 10.18632/oncotarget.6822
M3 - Article
C2 - 26741508
VL - 7
SP - 8771
EP - 8782
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 8
ER -