Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells.

Details

Serval ID
serval:BIB_BD376501B5A1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells.
Journal
The Journal of clinical investigation
Author(s)
Stanczak M.A., Siddiqui S.S., Trefny M.P., Thommen D.S., Boligan K.F., von Gunten S., Tzankov A., Tietze L., Lardinois D., Heinzelmann-Schwarz V., von Bergwelt-Baildon M., Zhang W., Lenz H.J., Han Y., Amos C.I., Syedbasha M., Egli A., Stenner F., Speiser D.E., Varki A., Zippelius A., Läubli H.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
01/11/2018
Peer-reviewed
Oui
Volume
128
Number
11
Pages
4912-4923
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.
Keywords
Antigens, CD/genetics, Antigens, CD/immunology, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic/immunology, Humans, Male, Neoplasm Proteins/genetics, Neoplasm Proteins/immunology, Neoplasms/genetics, Neoplasms/immunology, Neoplasms/mortality, Neoplasms/pathology, Polymorphism, Genetic, Sialic Acid Binding Immunoglobulin-like Lectins/genetics, Sialic Acid Binding Immunoglobulin-like Lectins/immunology, T-Lymphocytes/immunology, T-Lymphocytes/pathology, Cancer immunotherapy, Immunology, Oncology, T cells
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2018 19:32
Last modification date
18/09/2019 6:10
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