Universität zu Köln

Stanczak, Michal A., Siddiqui, Shoib S., Trefny, Marcel P., Thommen, Daniela S., Boligan, Kayluz Frias, von Gunten, Stephan ORCID: 0000-0002-2753-8738, Tzankov, Alexandar ORCID: 0000-0002-1100-3819, Tietze, Lothar, Lardinois, Didier, Heinzelmann-Schwarz, Viola ORCID: 0000-0002-4056-3225, von Bergwelt-Baildon, Michael, Zhang, Wu, Lenz, Heinz-Josef, Han, Younghun, Amos, Christopher I., Syedbasha, Mohammedyaseen, Egli, Adrian, Stenner, Frank ORCID: 0000-0003-4541-8817, Speiser, Daniel E., Varki, Ajit, Zippelius, Alfred and Laubli, Heinz (2018). Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells. J. Clin. Invest., 128 (11). S. 4912 - 4924. ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 1558-8238

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stanczak, Michal A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siddiqui, Shoib S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Trefny, Marcel P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thommen, Daniela S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boligan, Kayluz Frias UNSPECIFIED UNSPECIFIED UNSPECIFIED von Gunten, Stephan UNSPECIFIED orcid.org/0000-0002-2753-8738 UNSPECIFIED Tzankov, Alexandar UNSPECIFIED orcid.org/0000-0002-1100-3819 UNSPECIFIED Tietze, Lothar UNSPECIFIED UNSPECIFIED UNSPECIFIED Lardinois, Didier UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinzelmann-Schwarz, Viola UNSPECIFIED orcid.org/0000-0002-4056-3225 UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Wu UNSPECIFIED UNSPECIFIED UNSPECIFIED Lenz, Heinz-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED Han, Younghun UNSPECIFIED UNSPECIFIED UNSPECIFIED Amos, Christopher I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Syedbasha, Mohammedyaseen UNSPECIFIED UNSPECIFIED UNSPECIFIED Egli, Adrian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stenner, Frank UNSPECIFIED orcid.org/0000-0003-4541-8817 UNSPECIFIED Speiser, Daniel E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Varki, Ajit UNSPECIFIED UNSPECIFIED UNSPECIFIED Zippelius, Alfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Laubli, Heinz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-167999
DOI:	10.1172/JCI120612
Journal or Publication Title:	J. Clin. Invest.
Volume:	128
Number:	11
Page Range:	S. 4912 - 4924
Date:	2018
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	1558-8238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CD33-RELATED SIGLECS; INFLAMMATORY RESPONSES; BINDING SPECIFICITIES; LUNG-CANCER; CHECKPOINT; EXPRESSION; RECEPTORS; THERAPY; RECOGNITION; ENGAGEMENT Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16799