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01-09-2014 | Original Article

Intrinsically de-sialylated CD103⁺ CD8 T cells mediate beneficial anti-glioma immune responses

Authors: Emmanuel Jouanneau, Keith L. Black, Lucia Veiga, Ryan Cordner, Shyam Goverdhana, Yuying Zhai, Xiao-xue Zhang, Akanksha Panwar, Armen Mardiros, HongQiang Wang, Ashley Gragg, Mandana Zandian, Dwain K. Irvin, Christopher J. Wheeler

Published in: Cancer Immunology, Immunotherapy | Issue 9/2014

Abstract

Background

Cancer vaccines reproducibly cure laboratory animals and reveal encouraging trends in brain tumor (glioma) patients. Identifying parameters governing beneficial vaccine-induced responses may lead to the improvement of glioma immunotherapies. CD103⁺ CD8 T cells dominate post-vaccine responses in human glioma patients for unknown reasons, but may be related to recent thymic emigrant (RTE) status. Importantly, CD8 RTE metrics correlated with beneficial immune responses in vaccinated glioma patients.

Methods

We show by flow cytometry that murine and human CD103⁺ CD8 T cells respond better than their CD103⁻ counterparts to tumor peptide-MHC I (pMHC I) stimulation in vitro and to tumor antigens on gliomas in vivo.

Results

Glioma responsive T cells from mice and humans both exhibited intrinsic de-sialylation-affecting CD8 beta. Modulation of CD8 T cell sialic acid with neuraminidase and ST3Gal-II revealed de-sialylation was necessary and sufficient for promiscuous binding to and stimulation by tumor pMHC I. Moreover, de-sialylated status was required for adoptive CD8 T cells and lymphocytes to decrease GL26 glioma invasiveness and increase host survival in vivo. Finally, increased tumor ST3Gal-II expression correlated with clinical vaccine failure in a meta-analysis of high-grade glioma patients.

Conclusions

Taken together, these findings suggest that de-sialylation of CD8 is required for hyper-responsiveness and beneficial anti-glioma activity by CD8 T cells. Because CD8 de-sialylation can be induced with exogenous enzymes (and appears particularly scarce on human T cells), it represents a promising target for clinical glioma vaccine improvement.

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Title: Intrinsically de-sialylated CD103+ CD8 T cells mediate beneficial anti-glioma immune responses
Authors: Emmanuel Jouanneau
Keith L. Black
Lucia Veiga
Ryan Cordner
Shyam Goverdhana
Yuying Zhai
Xiao-xue Zhang
Akanksha Panwar
Armen Mardiros
HongQiang Wang
Ashley Gragg
Mandana Zandian
Dwain K. Irvin
Christopher J. Wheeler
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 9/2014
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-014-1559-2

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