University of Hertfordshire Research Archive

        JavaScript is disabled for your browser. Some features of this site may not work without it.

        Browse

        All of UHRABy Issue DateAuthorsTitlesThis CollectionBy Issue DateAuthorsTitles

        Arkivum Files

        My Downloads
        View Item 
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item

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

        View/Open
        120612.pdf (PDF, 4Mb)
        Author
        Stanczak, Michal A
        Siddiqui, Shoib S
        Trefny, Marcel P
        Thommen, Daniela S
        Boligan, Kayluz Frias
        von Gunten, Stephan
        Tzankov, Alexandar
        Tietze, Lothar
        Lardinois, Didier
        Heinzelmann-Schwarz, Viola
        von Bergwelt-Baildon, Michael
        Zhang, Wu
        Lenz, Heinz-Josef
        Han, Younghun
        Amos, Christopher I
        Syedbasha, Mohammedyaseen
        Egli, Adrian
        Stenner, Frank
        Speiser, Daniel E
        Varki, Ajit
        Zippelius, Alfred
        Läubli, Heinz
        Attention
        2299/24017
        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.
        Publication date
        2018-11-01
        Published in
        Journal of Clinical Investigation
        Published version
        https://doi.org/10.1172/JCI120612
        Other links
        http://hdl.handle.net/2299/24017
        Metadata
        Show full item record

        Related items

        Showing items related by title, author, creator and subject.

        • Completion of the sequence of the Aspergillus fumigatus partitivirus 1 genome. 

          Filippou, Charalampos; Coutts, Robert; Stevens, David A.; Sabino, Raquel; Kotta Loizou, Ioli (2020-05-27)
          A Portuguese isolate of Aspergillus fumigatus was found to contain three double-stranded (ds) RNA elements ranging in size from 1.1 to 1.8 kbp and comprising the genome of a strain of Aspergillus fumigatus partitivirus 1 ...
        • TGA2 signaling in response to reactive electrophile species is not dependent on cysteine modification of TGA2 

          Findling, Simone; Stotz, Henrik; Zoeller, Maria; Krischke, Markus; Zander, Mark; Gatz, Christiane; Berger, Susanne; Mueller, Martin J. (2018-04-02)
          Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation ...
        • Combining R gene and quantitative resistance increases effectiveness of cultivar resistance against Leptosphaeria maculans in Brassica napus in different environments : Combining R gene and quantitative resistance against Leptosphaeria maculans 

          Huang, Yongju; Mitrousia, Georgia; Mohamed Sidique, Siti; Qi, Aiming; Fitt, Bruce (2018-05-23)
          Using cultivar resistance against pathogens is one of the most economical and environmentally friendly methods for control of crop diseases. However, cultivar resistance can be easily rendered ineffective due to changes ...
        Keep in touch

        © 2019 University of Hertfordshire

        I want to...

        • Apply for a course
        • Download a Prospectus
        • Find a job at the University
        • Make a complaint
        • Contact the Press Office

        Go to...

        • Accommodation booking
        • Your student record
        • Bayfordbury
        • KASPAR
        • UH Arts

        The small print

        • Terms of use
        • Privacy and cookies
        • Criminal Finances Act 2017
        • Modern Slavery Act 2015
        • Sitemap

        Find/Contact us

        • T: +44 (0)1707 284000
        • E: ask@herts.ac.uk
        • Where to find us
        • Parking
        • hr
        • qaa
        • stonewall
        • AMBA
        • ECU Race Charter
        • disability confident
        • AthenaSwan