LIR-1 educates expanded human NK cells and defines a unique antitumor NK cell subset with potent antibody-dependent cellular cytotoxicity.

LIR‐1 NK cell education NK cells antibody‐dependent cellular cytotoxicity cancer immunotherapy

Journal

Clinical & translational immunology
ISSN: 2050-0068
Titre abrégé: Clin Transl Immunology
Pays: Australia
ID NLM: 101638268

Informations de publication

Date de publication:
2021
Historique:
received: 08 12 2020
revised: 01 09 2021
accepted: 16 09 2021
entrez: 11 10 2021
pubmed: 12 10 2021
medline: 12 10 2021
Statut: epublish

Résumé

KIR and NKG2A receptors educate human NK cells to stay responsive to cells with diminished HLA class I. Here, we addressed whether the HLA class I-binding receptor LIR-1 (LILRB1/ILT2/CD85j), which is widely expressed on human NK cells, can mediate education and contribute to antitumor functions of NK cells. Healthy donor NK cells either unstimulated, overnight cytokine-activated or We found that the inhibitory receptor LIR-1 can mediate NK cell education under specific conditions. This novel finding was exclusive to expanded NK cells and further characterisation of the cells revealed high expression of granzyme B and DNAM-1, which both previously have been linked to NK cell education. Corroborating the rheostat education model, LIR-1 co-expression with an educating KIR further increased the responsiveness of expanded NK cells. Inversely, antibody masking of LIR-1 decreased the responsiveness. LIR-1 These findings identify a unique NK cell subset attractive for adoptive cell therapy to treat cancer. Given that LIR-1 binds most HLA class I molecules, this subset may be explored in both autologous and allogeneic settings to innately reject HLA class I

Identifiants

pubmed: 34631057
doi: 10.1002/cti2.1346
pii: CTI21346
pmc: PMC8491220
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e1346

Informations de copyright

© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Déclaration de conflit d'intérêts

The authors declare no competing interest related to this work.

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Auteurs

Caroline Leijonhufvud (C)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.

Robert Reger (R)

Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda MD USA.

Filip Segerberg (F)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.

Jakob Theorell (J)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.
Oxford Autoimmune Neurology Group Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK.
Department of Clinical Neuroscience Centre for Molecular Medicine Karolinska Institute Karolinska University Hospital Stockholm Sweden.

Heinrich Schlums (H)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.

Yenan T Bryceson (YT)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.

Richard W Childs (RW)

Cellular and Molecular Therapeutics Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda MD USA.

Mattias Carlsten (M)

Department of Medicine Center for Hematology and Regenerative Medicine Karolinska Institutet Stockholm Sweden.
Center for Cell Therapy and Allogeneic Stem Cell Transplantation Karolinska University Hospital Sweden.

Classifications MeSH