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Tumor-Released Survivin Induces a Type-2T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro

Tumor-Released Survivin Induces a Type-2T Cell Response and Decreases Cytotoxic T Cell Function,... Clinical studies of T cell profiles from cancer patients have shown a skewing toward a type-2 T cell response with decreased cytotoxic T cell function. However, the primary cause of this shift remains unknown. Here we show that tumor-released Survivin, an inhibitor of apoptosis (IAP) protein and tumor-specific antigen, is taken up by T cells and alters their response. The addition of Survivin to T cell cultures resulted in decreased T cell proliferation and reduced cytotoxic CD8+ T cell function. Additionally, type 1 cell numbers and IFN-γ and IL-2 production were significantly reduced, while IL-4 release and type 2 T cell numbers increased. In contrast, the function and numbers of Th17 and T regulatory cells were not affected. These studies show that tumor-released Survivin modulates T cells resulting in a phenotype similar to that observed in cancer patients with a polarity shift from a type 1 to a type 2 response. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Microenvironment Springer Journals

Tumor-Released Survivin Induces a Type-2T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro

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References (58)

Publisher
Springer Journals
Copyright
Copyright © 2012 by Springer Science+Business Media B.V.
Subject
Biomedicine; Cancer Research; Oncology; Immunology; Cell Biology; Biochemistry, general; Biomedicine general
ISSN
1875-2292
eISSN
1875-2284
DOI
10.1007/s12307-012-0096-9
pmid
22322461
Publisher site
See Article on Publisher Site

Abstract

Clinical studies of T cell profiles from cancer patients have shown a skewing toward a type-2 T cell response with decreased cytotoxic T cell function. However, the primary cause of this shift remains unknown. Here we show that tumor-released Survivin, an inhibitor of apoptosis (IAP) protein and tumor-specific antigen, is taken up by T cells and alters their response. The addition of Survivin to T cell cultures resulted in decreased T cell proliferation and reduced cytotoxic CD8+ T cell function. Additionally, type 1 cell numbers and IFN-γ and IL-2 production were significantly reduced, while IL-4 release and type 2 T cell numbers increased. In contrast, the function and numbers of Th17 and T regulatory cells were not affected. These studies show that tumor-released Survivin modulates T cells resulting in a phenotype similar to that observed in cancer patients with a polarity shift from a type 1 to a type 2 response.

Journal

Cancer Microenvironment – Springer Journals

Published: Feb 10, 2012

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