Siglec-9 Regulates an Effector Memory CD8<sup>+</sup> T-cell Subset That Congregates in the Melanoma Tumor Microenvironment.

Details

Serval ID
serval:BIB_AA99A510B25F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Siglec-9 Regulates an Effector Memory CD8<sup>+</sup> T-cell Subset That Congregates in the Melanoma Tumor Microenvironment.
Journal
Cancer immunology research
Author(s)
Haas Q., Boligan K.F., Jandus C., Schneider C., Simillion C., Stanczak M.A., Haubitz M., Seyed Jafari S.M., Zippelius A., Baerlocher G.M., Läubli H., Hunger R.E., Romero P., Simon H.U., von Gunten S.
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
Published
Issued date
05/2019
Peer-reviewed
Oui
Volume
7
Number
5
Pages
707-718
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Emerging evidence suggests an immunosuppressive role of altered tumor glycosylation due to downregulation of innate immune responses via immunoregulatory Siglecs. In contrast, human T cells, a major anticancer effector cell, only rarely express Siglecs. However, here, we report that the majority of intratumoral, but not peripheral blood, cytotoxic CD8 <sup>+</sup> T cells expressed Siglec-9 in melanoma. We identified Siglec-9 <sup>+</sup> CD8 <sup>+</sup> T cells as a subset of effector memory cells with high functional capacity and signatures of clonal expansion. This cytotoxic T-cell subset was functionally inhibited in the presence of Siglec-9 ligands or by Siglec-9 engagement by specific antibodies. TCR signaling pathways and key effector functions (cytotoxicity, cytokine production) of CD8 <sup>+</sup> T cells were suppressed by Siglec-9 engagement, which was associated with the phosphorylation of the inhibitory protein tyrosine phosphatase SHP-1, but not SHP-2. Expression of cognate Siglec-9 ligands was observed on the majority of tumor cells in primary and metastatic melanoma specimens. Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment.
Pubmed
Web of science
Open Access
Yes
Create date
28/04/2019 15:43
Last modification date
20/08/2019 16:14
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