Universität zu Köln

Weil, Sandra, Memmer, Stefanie, Lechner, Axel, Huppert, Volker, Giannattasio, Ariane, Becker, Tamara, Mueller-Runte, Andreas, Lampe, Karen, Beutner, Dirk, Quaas, Alexander, Schubert, Ralf, Herrmann, Eva, Steinle, Alexander ORCID: 0000-0001-5081-8503, Koehl, Ulrike, Walter, Lutz ORCID: 0000-0001-9408-3131, von Bergwelt-Baildon, Michael S. and Koch, Joachim (2017). Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma. Front. Immunol., 8. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs). Based on plasma and tumor samples of 44 HNSCC patients, we found that despite compositional heterogeneity the total plasma level of NKG2DLs correlates with NK cell inhibition and disease progression. Strikingly, based on tumor spheroids and primary tumors of HNSCC patients, we found that NK cells failed to infiltrate HNSCC tumors in the presence of high levels of NKG2DLs, demonstrating a novel mechanism of NKG2DL-dependent tumor immune escape. Therefore, the diagnostic acquisition of the plasma level of all NKG2DLs might be instrumental for prognosis and to decipher a patient cohort, which could benefit from restoration of NKG2D-dependent tumor immunosurveillance. Along these lines, we could show that removal of shed NKG2DLs (sNKG2DLs) from HNSCC patients' plasma restored NK cell function in vitro and in individual patients following surgical removal of the primary tumor. In order to translate these findings into a therapeutic setting, we performed a proof-of-concept study to test the efficacy of adsorption apheresis of sNKG2DLs from plasma after infusion of human MICA in rhesus monkeys. Complete removal of MICA was achieved after three plasma volume exchanges. Therefore, we propose adsorption apheresis of sNKG2DLs as a future preconditioning strategy to improve the efficacy of autologous and adoptively transferred immune cells in cellular cancer immunotherapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weil, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Memmer, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechner, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Huppert, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Giannattasio, Ariane UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller-Runte, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lampe, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Beutner, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinle, Alexander UNSPECIFIED orcid.org/0000-0001-5081-8503 UNSPECIFIED Koehl, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Lutz UNSPECIFIED orcid.org/0000-0001-9408-3131 UNSPECIFIED von Bergwelt-Baildon, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-234045
DOI:	10.3389/fimmu.2017.00387
Journal or Publication Title:	Front. Immunol.
Volume:	8
Date:	2017
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN NK CELLS; PROGNOSTIC-SIGNIFICANCE; HUMAN-PAPILLOMAVIRUS; T-CELLS; PERIPHERAL-BLOOD; DISEASE STAGE; SOLUBLE MICA; HUMAN NKG2D; TUMOR; EXPRESSION Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23404