Steinle Lab

2020

MICAgen Mice Recapitulate the Highly Restricted but Activation-Inducible Expression of the Paradigmatic Human NKG2D Ligand MICA
Kim Y; Born C; Bléry M; Steinle A.
Front. Immunol., 04 June 2020; Article 960

Editorial: ADAM10 in Cancer Immunology and Autoimmunity: More Than a Simple Biochemical Scissor
Rossello A; Steinle A; Poggi A; Zocchi MR.
Front. Immunol., July 2020; Article 1483

Arming Cytotoxic Lymphocytes for Cancer Immunotherapy by Means of the NKG2D/NKG2D-Ligand System.
Lazarova M, Wels WS, Steinle A.
Expert Opin Biol Ther. 2020 Jul 29.


2019

Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion.
Paczulla AM, Rothfelder K, Raffel S, Konantz M, Steinbacher J, Wang H, Tandler C, Mbarga M, Schaefer T, Falcone M, Nievergall E, Dörfel D, Hanns P, Passweg JR, Lutz C, Schwaller J, Zeiser R, Blazar BR, Caligiuri MA, Dirnhofer S, Lundberg P, Kanz L, Quintanilla-Martinez L, Steinle A, Trumpp A, Salih HR, Lengerke C.
Nature. 2019;572(7768):254-259.

The NKG2D axis: an emerging target in cancer immunotherapy.
Lazarova M, Steinle A.
Expert Opin Ther Targets. 2019;23(4):281-294.

Impairment of NKG2D-Mediated Tumor Immunity by TGF-β.
Lazarova M, Steinle A.
Front Immunol. 2019;10:2689. Review.

CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML.
Salomé B, Gomez-Cadena A, Loyon R, Suffiotti M, Salvestrini V, Wyss T, Vanoni G, Ruan DF, Rossi M, Tozzo A, Tentorio P, Bruni E, Riether C, Jacobsen EM, Jandus P, Conrad C, Hoenig M, Schulz A, Michaud K, Della Porta MG, Salvatore S, Ho PC, Gfeller D, Ochsenbein A, Mavilio D, Curti A, Marcenaro E, Steinle A, Horowitz A, Romero P, Trabanelli S, Jandus C.
Blood Adv. 2019;3(22):3674-3687.


2018

Cutting an NKG2D Ligand Short: Cellular Processing of the Peculiar Human NKG2D Ligand ULBP4.
Zöller T, Wittenbrink M, Hoffmeister M, Steinle A.
Front Immunol. 2018;9:620.

The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma.
Kropp KN, Maurer S, Rothfelder K, Schmied BJ, Clar KL, Schmidt M, Strunz B, Kopp HG, Steinle A, Grünebach F, Rittig SM, Salih HR, Dörfel D.
Cancer Immunol Immunother. 2018;67:935-947.

Pillars Article: Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA. Science. 1999. 285: 727-729.
Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T.
J Immunol. 2018;200:2231-2233.

Select Clr-g Expression on Activated Dendritic Cells Facilitates Cognate Interaction with a Minor Subset of Splenic NK Cells Expressing the Inhibitory Nkrp1g Receptor.
Friede ME, Leibelt S, Dudziak D, Steinle A.
J Immunol. 2018;200:983-996. 

NKG2D-Dependent Antitumor Effects of Chemotherapy and Radiotherapy against Glioblastoma.
Weiss T, Schneider H, Silginer M, Steinle A, Pruschy M, Polić B, Weller M, Roth P.
Clin Cancer Res. 2018;24:882-895.

Maurer S, Kropp KN, Klein G, Steinle A, Haen SP, Walz, JS, Hinterleitner C, Märklin M, Kopp H-G, Salih HR.
Oncoimmunology. 2018;7:e1364827.

Almeida FF, Tognarelli S, Marçais A, Kueh AJ, Friede ME, Liao Y, Willis SN, Luong K, Faure F, Mercier FE, Galluso J, Firth M, Narni-Mancinelli E, Rais B, Scadden DT, Spallotta F, Weil S, Giannattasio A, Kalensee F, Zöller T, Huntington ND, Schleicher U, Chiocchetti AG, Ugolini S, Herold MJ, Shi W, Koch J, Steinle A, Vivier E, Walzer T, Belz GT, Ullrich E.
Oncoimmunology. 2018;7:e1475875.

Neuss S, Bartel Y, Born C, Weil S, Koch J, Behrends C, Hoffmeister M, Steinle A.
J Immunol. 2018;201:1275-1286. 

2017

HemITAM: A single tyrosine motif that packs a punch.
Bauer B, Steinle A.
Sci Signal. 2017;10.

Chronic NKG2D Engagement In Vivo Differentially Impacts NK Cell Responsiveness by Activating NK Receptors.
Koch C, Kim Y, Zöller T, Born C, Steinle A.
Front Immunol. 2017;8:1466.

Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma.
Weil S, Memmer S, Lechner A, Huppert V, Giannattasio A, Becker T, Müller-Runte A, Lampe K, Beutner D, Quaas A, Schubert R, Herrmann E, Steinle A, Koehl U, Walter L, von Bergwelt-Baildon MS, Koch J.
Front Immunol. 2017;8:387.

Bauer B, Wotapek T, Zöller T, Rutkowski E, Steinle A.
J Biol Chem. 2017;292:3213-3223.

Rutkowski E, Leibelt S, Born C, Friede ME, Bauer S, Weil S, Koch J, Steinle A.
J Immunol. 2017;198:916-926.


2016

The stalk domain of NKp30 contributes to ligand binding and signaling of a pre-assembled NKp30/CD3ζ complex.
Memmer S, Weil S, Beyer S, Zöller T, Peters E, Hartmann J, Steinle A, Koch J.
J Biol Chem. 2016;291:25427-25438.

Human hematopoietic CD34+ progenitor cells induce natural killer cell alloresponses via NKG2D activation.
Ulbar F, Nicolini B, Chirumbolo G, Tolomelli G, Steinle A, Rondelli D, Arpinati M.
Exp Hematol. 2016;44:14-23.


2015

Dedicated immunosensing of the mouse intestinal epithelium facilitated by a pair of genetically coupled lectin-like receptors.
Leibelt S, Friede ME, Rohe C, Gütle D, Rutkowski E, Weigert A, Kveberg L, Vaage JT,
Hornef MW, Steinle A.
Mucosal Immunol. 2015;8:232-42.

Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65.
Bauer B, Spreu J, Rohe C, Vogler I, Steinle A.
Immunology 2015;145:114-23.

MULT1plying cancer immunity.
Steinle A, Cerwenka A.
Science 2015;348:45-6.

An Fc-optimized NKG2D-immunoglobulin G fusion protein for induction of natural killer cell reactivity against leukemia.
Steinbacher J, Baltz-Ghahremanpour K, Schmiedel BJ, Steinle A, Jung G, Kübler A, André MC, Grosse-Hovest L, Salih HR.
Int J Cancer 2015;136:1073-84.

Cytotoxicity and infiltration of human NK cells in in vivo-like tumor spheroids.
Giannattasio A, Weil S, Kloess S, Ansari N, Stelzer EH, Cerwenka A, Steinle A, Koehl U, Koch J.
BMC Cancer 2015;15:351.


2014

Transferrin' activation: Bonding with transferrin receptors tunes KLRG1 function.
Steinle A.
Eur J Immunol. 2014;44:1600-3.

A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells.
Wolpert F, Tritschler I, Steinle A, Weller M, Eisele G.
Neuro Oncol. 2014;16:382-91.

Fc-Optimized NKG2D-Fc Constructs Induce NK Cell Antibody-Dependent Cellular Cytotoxicity against Breast Cancer Cells Independently of HER2/neu Expression Status.
Raab S, Steinbacher J, Schmiedel BJ, Kousis PC, Steinle A, Jung G, Grosse-Hovest L, Salih HR.
J Immunol. 2014;193:4261-72.

MicroRNA-mediated down-regulation of NKG2D ligands contributes to glioma immune escape.
Codo P, Weller M, Meister G, Szabo E, Steinle A, Wolter M, Reifenberger G, Roth P.
Oncotarget 2014;5:7651-62.

Altered microRNA expression after infection with human cytomegalovirus leads to TIMP3 downregulation and increased shedding of metalloprotease substrates, including MICA.
Esteso G, Luzón E, Sarmiento E, Gómez-Caro R, Steinle A, Murphy G, Carbone J, Valés-Gómez M, Reyburn HT.
J Immunol. 2014;193:1344-52.


2013


2012

Impaired tumor rejection by memory CD8 T cells in mice with NKG2D dysfunction.
André MC, Sigurdardottir D, Kuttruff S, Pömmerl B, Handgretinger R, Rammensee HG, Steinle A.
Int J Cancer. 2012;131:1601-10.

Comprehensive analysis of NKG2D ligand expression and release in leukemia: implications for NKG2D-mediated NK cell responses.
Hilpert J, Grosse-Hovest L, Grünebach F, Buechele C, Nuebling T, Raum T, Steinle A, Salih HR.
J Immunol. 2012;189:1360-71.

Tumor suppressive microRNAs miR-34a/c control cancer cell expression of ULBP2, a stress-induced ligand of the natural killer cell receptor NKG2D.
Heinemann A, Zhao F, Pechlivanis S, Eberle J, Steinle A, Diederichs S, Schadendorf D, Paschen A.
Cancer Res. 2012;72:460-71.


2011

Cutting edge: NKp80 uses an atypical hemi-ITAM to trigger NK cytotoxicity.
Dennehy KM, Klimosch SN, Steinle A.
J Immunol. 2011;186:657-61.

The polymorphic HCMV glycoprotein UL20 is targeted for lysosomal degradation by multiple cytoplasmic dileucine motifs.
Jelcic I, Reichel J, Schlude C, Treutler E, Sinzger C, Steinle A.
Traffic. 2011;12:1444-56.

Vis-à-Vis in the NKC: genetically linked natural killer cell receptor/ligand pairs in the Natural Killer Gene complex (NKC).
Vogler I, Steinle A.
J Innate Immun. 2011;3:227-35.


2010

Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes.
Spreu J, Kuttruff S, Stejfova V, Dennehy KM, Schittek B, Steinle A.
Proc Natl Acad Sci U S A. 2010;107:5100-5.

Structure of the HCMV UL16-MICB complex elucidates select binding of a viral immunoevasin to diverse NKG2D ligands.
Müller S, Zocher G, Steinle A, Stehle T.
PLoS Pathog. 2010;6:e1000723.

Conserved amino acids within the adenovirus 2 E3/19K protein differentially affect downregulation of MHC class I and MICA/B proteins.
Sester M, Koebernick K, Owen D, Ao M, Bromberg Y, May E, Stock E, Andrews L, Groh V, Spies T, Steinle A, Menz B, Burgert HG.
J Immunol. 2010;184:255-67.

The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity.
Salih J, Hilpert J, Placke T, Grünebach F, Steinle A, Salih HR, Krusch M.
Int J Cancer. 2010;127:2119-28.


2002-2009 (University of Tübingen)

2009

NKp80 defines and stimulates a reactive subset of CD8 T cells.
Kuttruff S, Koch S, Kelp A, Pawelec G, Rammensee HG, Steinle A.
Blood. 2009;113:358-69.

Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain.
Wittenbrink M, Spreu J, Steinle A.
Eur J Immunol. 2009;39:1642-51.

Reinforcing natural killers.
Salih HR, Steinle A.
Blood. 2009;113:6042-3.

Differential clinical significance of individual NKG2D ligands in melanoma: soluble ULBP2 as an indicator of poor prognosis superior to S100B.
Paschen A, Sucker A, Hill B, Moll I, Zapatka M, Nguyen XD, Sim GC, Gutmann I, Hassel J, Becker JC, Steinle A, Schadendorf D, Ugurel S.
Clin Cancer Res. 2009;15:5208-15.

Interferon-gamma down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells.
Schwinn N, Vokhminova D, Sucker A, Textor S, Striegel S, Moll I, Nausch N, Tuettenberg J, Steinle A, Cerwenka A, Schadendorf D, Paschen A.
Int J Cancer. 2009;124:1594-604.

2008

Tumor-associated MICA is shed by ADAM proteases.
Waldhauer I, Goehlsdorf D, Gieseke F, Weinschenk T, Wittenbrink M, Ludwig A, Stevanovic S, Rammensee HG, Steinle A.
Cancer Res. 2008;68:6368-76.

NK cells and cancer immunosurveillance. 
Waldhauer I, Steinle A.
Oncogene. 2008;27:5932-43.

Soluble NKG2D ligands: prevalence, release, and functional impact. 
Salih HR, Holdenrieder S, Steinle A.
Front Biosci. 2008;13:3448-56.

Interaction of monocytes with NK cells upon Toll-like receptor-induced expression of the NKG2D ligand MICA.
Kloss M, Decker P, Baltz KM, Baessler T, Jung G, Rammensee HG, Steinle A, Krusch M, Salih HR.
J Immunol. 2008;181:6711-9.

Direct and natural killer cell-mediated antitumor effects of low-dose bortezomib in hepatocellular carcinoma.
Armeanu S, Krusch M, Baltz KM, Weiss TS, Smirnow I, Steinle A, Lauer UM, Bitzer M, Salih HR.
Clin Cancer Res. 2008;14:3520-8.

Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D.
Krockenberger M, Dombrowski Y, Weidler C, Ossadnik M, Hönig A, Häusler S, Voigt H, Becker JC, Leng L, Steinle A, Weller M, Bucala R, Dietl J, Wischhusen J.
J Immunol. 2008;180:7338-48.

2007

CLEC2A: a novel, alternatively spliced and skin-associated member of the NKC-encoded AICL-CD69-LLT1 family.
Spreu J, Kienle EC, Schrage B, Steinle A.
Immunogenetics. 2007;59:903-12.

Soluble NKG2D ligands in hepatic autoimmune diseases and in benign diseases involved in marker metabolism.
Holdenrieder S, Eichhorn P, Beuers U, Samtleben W, Stieber P, Nagel D, Peterfi A, Steinle A, Salih HR.
Anticancer Res. 2007;27:2041-5.

2006

Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction.
Welte S, Kuttruff S, Waldhauer I, Steinle A.
Nat Immunol. 2006;7:1334-42.

Proteolytic release of soluble UL16-binding protein 2 from tumor cells.
Waldhauer I, Steinle A.
Cancer Res. 2006;66:2520-6.

Human cytomegalovirus-encoded UL16 discriminates MIC molecules by their alpha2 domains.
Spreu J, Stehle T, Steinle A.       
J Immunol. 2006;177:3143-9.

Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients.
Salih HR, Goehlsdorf D, Steinle A.
Hum Immunol. 2006;67:188-95.

Soluble MICA in malignant diseases.
Holdenrieder S, Stieber P, Peterfi A, Nagel D, Steinle A, Salih HR.
Int J Cancer. 2006;118:684-7.

Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA.
Holdenrieder S, Stieber P, Peterfi A, Nagel D, Steinle A, Salih HR.
Cancer Immunol Immunother. 2006;55:1584-9.

TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells.
Eisele G, Wischhusen J, Mittelbronn M, Meyermann R, Waldhauer I, Steinle A, Weller M, Friese MA.
Brain. 2006;129:2416-25.

Natural killer cell-mediated rejection of experimental human lung cancer by genetic overexpression of major histocompatibility complex class I chain-related gene A.
Busche A, Goldmann T, Naumann U, Steinle A, Brandau S.
Hum Gene Ther. 2006;17:135-46.

2005

Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo.
Wiemann K, Mittrücker HW, Feger U, Welte SA, Yokoyama WM, Spies T, Rammensee HG, Steinle A.
J Immunol. 2005;175:720-9.

Natural killer cell-mediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate.
Armeanu S, Bitzer M, Lauer UM, Venturelli S, Pathil A, Krusch M, Kaiser S, Jobst J, Smirnow I, Wagner A, Steinle A, Salih HR.
Cancer Res. 2005;65:6321-9.

Activation of V gamma 9V delta 2 T cells by NKG2D.
Rincon-Orozco B, Kunzmann V, Wrobel P, Kabelitz D, Steinle A, Herrmann T.
J Immunol. 2005;175:2144-51.

Danger-Detector NKG2D: Immunosurveillance of Induced Self and Modulation by Cytokines and Soluble Ligands.
Wiemann K and Steinle A.
Current Medicinal Chemistry – Anti-Inflammatory & Anti-Allergy Agents 2005;4:141-152.

2004

RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo.
Friese MA, Wischhusen J, Wick W, Weiler M, Eisele G, Steinle A, Weller M.
Cancer Res. 2004;64:7596-603.

Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer.
Wu JD, Higgins LM, Steinle A, Cosman D, Haugk K, Plymate SR.
J Clin Invest. 2004;114:560-8.

Vdelta1 T lymphocytes from B-CLL patients recognize ULBP3 expressed on leukemic B cells and up-regulated by trans-retinoic acid.
Poggi A, Venturino C, Catellani S, Clavio M, Miglino M, Gobbi M, Steinle A, Ghia P, Stella S, Caligaris-Cappio F, Zocchi MR.
Cancer Res. 2004;64:9172-9.

Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma.
Raffaghello L, Prigione I, Airoldi I, Camoriano M, Levreri I, Gambini C, Pende D, Steinle A, Ferrone S, Pistoia V.
Neoplasia. 2004;6:558-68.

2003

Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia.
Salih HR, Antropius H, Gieseke F, Lutz SZ, Kanz L, Rammensee HG, Steinle A.
Blood. 2003;102:1389-96. Epub 2003 Apr 24.

Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein.
Welte SA, Sinzger C, Lutz SZ, Singh-Jasuja H, Sampaio KL, Eknigk U, Rammensee HG, Steinle A.
Eur J Immunol. 2003;33:194-203.

MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
Friese MA, Platten M, Lutz SZ, Naumann U, Aulwurm S, Bischof F, Bühring HJ, Dichgans J, Rammensee HG, Steinle A, Weller M.
Cancer Res. 2003;63:8996-9006.

2002

Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding.
Salih HR, Rammensee HG, Steinle A.
J Immunol. 2002;169:4098-102.


1998-2001 (Fred Hutchinson Cancer Research Center Seattle/Spies Lab)

2001

Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family.
Steinle A, Li P, Morris DL, Groh V, Lanier LL, Strong RK, Spies T.
Immunogenetics. 2001;53:279-87.

Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA.
Li P, Morris DL, Willcox BE, Steinle A, Spies T, Strong RK.
Nat Immunol. 2001;2:443-51.

1999

Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.
Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T.
Science. 1999;285:727-9.

1998

Diversification, expression, and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules.
Steinle A, Groh V, Spies T.
Proc Natl Acad Sci U S A. 1998;95:12510-5.

Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells.
Groh V, Steinle A, Bauer S, Spies T.
Science. 1998;279:1737-40.


1992-1997 (University of Munich/Schendel Lab)

1997

Cytolytic T lymphocyte recognition of the immunodominant HLA-A*0201-restricted Melan-A/MART-1 antigenic peptide in melanoma.
Romero P1, Gervois N, Schneider J, Escobar P, Valmori D, Pannetier C, Steinle A, Wolfel T, Lienard D, Brichard V, van Pel A, Jotereau F, Cerottini JC.
J Immunol. 1997;159:2366-74.

1996

Motif of HLA-B*3503 peptide ligands.
Steinle A, Falk K, Rötzschke O, Gnau V, Stevanović S, Jung G, Schendel DJ, Rammensee HG.
Immunogenetics. 1996;43:105-7. No abstract available.

The HLA likes and dislikes of allospecific and non-MHC-restricted cytotoxic T lymphocytes.
Nössner E, Falk CS, Jantzer P, Reinhardt C, Steinle A, Schendel DJ.
Immunol Rev. 1996;154:105-35. No abstract available.

1995

In vivo expansion of HLA-B35 alloreactive T cells sharing homologous T cell receptors: evidence for maintenance of an oligoclonally dominated allospecificity by persistent stimulation with an autologous MHC/peptide complex.
Steinle A, Reinhardt C, Jantzer P, Schendel DJ.
J Exp Med. 1995;181:503-13.

Expression of HLA-C molecules confers target cell resistance to some non-major histocompatibility complex-restricted T cells in a manner analogous to allospecific natural killer cells.
Falk CS, Steinle A, Schendel DJ.
J Exp Med. 1995;182:1005-18.

1994

HLA class I alleles of LCL 721 and 174 x CEM.T2 (T2).
Steinle A, Schendel DJ.
Tissue Antigens. 1994;44:268-70.

HLA-DQ-restricted, islet-specific T-cell clones of a type I diabetic patient. T-cell receptor sequence similarities to insulitis-inducing T-cells of nonobese diabetic mice.
Durinovic-Bellò I, Steinle A, Ziegler AG, Schendel DJ.
Diabetes. 1994;43:1318-25.

MHC class I allorecognition: the likes and dislikes of CTL and NK cells. 
Reinhardt C, Falk C, Steinle A, Schendel DJ.
Behring Inst Mitt. 1994;94:61-71.

1993

Microheterogeneity in HLA-B35 alleles influences peptide-dependent allorecognition by cytotoxic T cells but not binding of a peptide-restricted monoclonal antibody.
Steinle A1, Reinhardt C, Nössner E, Uchanska-Ziegler B, Ziegler A, Schendel DJ.
Hum Immunol. 1993;38:261-9.

1992

Cytotoxic T lymphocytes show HLA-C-restricted recognition of EBV-bearing cells and allorecognition of HLA class I molecules presenting self-peptides.
Schendel DJ, Reinhardt C, Nelson PJ, Maget B, Pullen L, Bornkamm GW, Steinle A.
J Immunol. 1992;149:2406-14.

Isolation and characterization of a genomic HLA-Cw6 clone.
Steinle A, Nössner E, Schendel DJ.
Tissue Antigens. 1992;39:134-7.