en
Scientific article
English

Siglec-9 regulates an effector memory CD8+ T-cell subset that congregates in the melanoma tumor microenvironment

Published inCancer Immunology Research, vol. 7, no. 5, p. 707-718
Publication date2019
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+ T cells expressed Siglec-9 in melanoma. We identified Siglec-9+ CD8+ 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+ 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.

Affiliation Not a UNIGE publication
Citation (ISO format)
HAAS, Quentin et al. Siglec-9 regulates an effector memory CD8+ T-cell subset that congregates in the melanoma tumor microenvironment. In: Cancer Immunology Research, 2019, vol. 7, n° 5, p. 707–718. doi: 10.1158/2326-6066.CIR-18-0505
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal2326-6066
182views
0downloads

Technical informations

Creation2020/05/04 21:47:00
First validation2020/05/04 21:47:00
Update time2023/03/15 21:56:26
Status update2023/03/15 21:56:25
Last indexation2024/01/17 09:50:55
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack