Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)8771-82
Number of pages12
JournalOncotarget
Volume7
Issue number8
DOIs
Publication statusPublished - 23 Feb 2016

Cite this

Perdicchio, Maurizio ; Cornelissen, Lenneke A M ; Streng-Ouwehand, Ingeborg ; Engels, Steef ; Verstege, Marleen I ; Boon, Louis ; Geerts, Dirk ; van Kooyk, Yvette ; Unger, Wendy W J. / Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells. In: Oncotarget. 2016 ; Vol. 7, No. 8. pp. 8771-82.
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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.",
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author = "Maurizio Perdicchio and Cornelissen, {Lenneke A M} and Ingeborg Streng-Ouwehand and Steef Engels and Verstege, {Marleen I} and Louis Boon and Dirk Geerts and {van Kooyk}, Yvette and Unger, {Wendy W J}",
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Perdicchio, M, Cornelissen, LAM, Streng-Ouwehand, I, Engels, S, Verstege, MI, Boon, L, Geerts, D, van Kooyk, Y & Unger, WWJ 2016, 'Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells' Oncotarget, vol. 7, no. 8, pp. 8771-82. https://doi.org/10.18632/oncotarget.6822

Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells. / Perdicchio, Maurizio; Cornelissen, Lenneke A M; Streng-Ouwehand, Ingeborg; Engels, Steef; Verstege, Marleen I; Boon, Louis; Geerts, Dirk; van Kooyk, Yvette; Unger, Wendy W J.

In: Oncotarget, Vol. 7, No. 8, 23.02.2016, p. 8771-82.

Research output: Contribution to journalArticleAcademicpeer-review

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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

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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.

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KW - Apoptosis

KW - Blotting, Western

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KW - Cell Cycle

KW - Cell Movement

KW - Cell Proliferation

KW - Flow Cytometry

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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

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SP - 8771

EP - 8782

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

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