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
Institution
Title
Siglec-9 Regulates an Effector Memory CD8<sup>+</sup> T-cell Subset That Congregates in the Melanoma Tumor Microenvironment.
Journal
Cancer immunology research
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 ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Antigens, CD/immunology, CD8-Positive T-Lymphocytes/immunology, Cell Line, Tumor, Humans, Melanoma/immunology, Sialic Acid Binding Immunoglobulin-like Lectins/immunology, T-Lymphocyte Subsets/immunology, Tumor Microenvironment/immunology
Pubmed
Web of science
Open Access
Yes
Create date
28/04/2019 15:43
Last modification date
12/08/2020 6:22