dc.contributor.author | Stanczak, Michal A | |
dc.contributor.author | Siddiqui, Shoib S | |
dc.contributor.author | Trefny, Marcel P | |
dc.contributor.author | Thommen, Daniela S | |
dc.contributor.author | Boligan, Kayluz Frias | |
dc.contributor.author | von Gunten, Stephan | |
dc.contributor.author | Tzankov, Alexandar | |
dc.contributor.author | Tietze, Lothar | |
dc.contributor.author | Lardinois, Didier | |
dc.contributor.author | Heinzelmann-Schwarz, Viola | |
dc.contributor.author | von Bergwelt-Baildon, Michael | |
dc.contributor.author | Zhang, Wu | |
dc.contributor.author | Lenz, Heinz-Josef | |
dc.contributor.author | Han, Younghun | |
dc.contributor.author | Amos, Christopher I | |
dc.contributor.author | Syedbasha, Mohammedyaseen | |
dc.contributor.author | Egli, Adrian | |
dc.contributor.author | Stenner, Frank | |
dc.contributor.author | Speiser, Daniel E | |
dc.contributor.author | Varki, Ajit | |
dc.contributor.author | Zippelius, Alfred | |
dc.contributor.author | Läubli, Heinz | |
dc.date.accessioned | 2021-03-04T11:30:02Z | |
dc.date.available | 2021-03-04T11:30:02Z | |
dc.date.issued | 2018-11-01 | |
dc.identifier.citation | 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 2018 , ' Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells ' , Journal of Clinical Investigation , vol. 128 , no. 11 , pp. 4912-4923 . https://doi.org/10.1172/JCI120612 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.other | PubMedCentral: PMC6205408 | |
dc.identifier.uri | http://hdl.handle.net/2299/24017 | |
dc.description | © 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612 | |
dc.description.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. | en |
dc.format.extent | 13 | |
dc.format.extent | 5133064 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Clinical Investigation | |
dc.subject | Antigens, CD/genetics | |
dc.subject | Cell Line, Tumor | |
dc.subject | Female | |
dc.subject | Gene Expression Regulation, Neoplastic/immunology | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Neoplasm Proteins/genetics | |
dc.subject | Neoplasms/genetics | |
dc.subject | Polymorphism, Genetic | |
dc.subject | Sialic Acid Binding Immunoglobulin-like Lectins/genetics | |
dc.subject | T-Lymphocytes/immunology | |
dc.title | Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Future Societies Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1172/JCI120612 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |