A Variant of a Killer Cell Immunoglobulin-like Receptor Is Associated with Resistance to PD-1 Blockade in Lung Cancer.


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
15 05 2019
Historique:
received: 16 09 2018
revised: 14 12 2018
accepted: 04 02 2019
pubmed: 16 2 2019
medline: 17 7 2020
entrez: 16 2 2019
Statut: ppublish

Résumé

PD-(L)1-blocking antibodies have clinical activity in metastatic non-small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways. Peripheral blood mononuclear cells were collected from 35 patients with NSCLC receiving nivolumab monotherapy. Cellular changes, cytokine levels, gene expression, and polymorphisms were compared between responders and nonresponders to treatment. Findings were confirmed in additional cohorts of patients with NSCLC receiving immune checkpoint blockade. We identified a genetic variant of a killer cell immunoglobulin-like receptor (KIR) We identified an association of the

Identifiants

pubmed: 30765392
pii: 1078-0432.CCR-18-3041
doi: 10.1158/1078-0432.CCR-18-3041
doi:

Substances chimiques

KIR3DS1 protein, human 0
PDCD1 protein, human 0
Programmed Cell Death 1 Receptor 0
Receptors, KIR3DS1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3026-3034

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Marcel P Trefny (MP)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Sacha I Rothschild (SI)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Department of Internal Medicine, Division of Oncology, University Hospital Basel, Basel, Switzerland.

Franziska Uhlenbrock (F)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Dietmar Rieder (D)

Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Benjamin Kasenda (B)

Department of Internal Medicine, Division of Oncology, University Hospital Basel, Basel, Switzerland.

Michal A Stanczak (MA)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Fiamma Berner (F)

Institute of Immunobiology and Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Abhishek S Kashyap (AS)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Monika Kaiser (M)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Petra Herzig (P)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.

Severin Poechtrager (S)

Cantonal Hospital Liestal, Liestal, Switzerland.

Daniela S Thommen (DS)

Division of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Florian Geier (F)

Department of Biomedicine, Division of Bioinformatics, University Hospital and University of Basel, Basel, Switzerland.

Spasenija Savic (S)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Philip Jermann (P)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Ilaria Alborelli (I)

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Stefan Schaub (S)

HLA-Diagnostic & Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

Frank Stenner (F)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Department of Internal Medicine, Division of Oncology, University Hospital Basel, Basel, Switzerland.

Martin Früh (M)

Department of Medical Oncology/Hematology, Cantonal Hospital of St. Gallen, St. Gallen and University of Bern, Bern, Switzerland.

Zlatko Trajanoski (Z)

Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Lukas Flatz (L)

Institute of Immunobiology and Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Kirsten D Mertz (KD)

Cantonal Hospital Liestal, Liestal, Switzerland.

Alfred Zippelius (A)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland. heinz.laeubli@unibas.ch alfred.zippelius@usb.ch.
Department of Internal Medicine, Division of Oncology, University Hospital Basel, Basel, Switzerland.

Heinz Läubli (H)

Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland. heinz.laeubli@unibas.ch alfred.zippelius@usb.ch.
Department of Internal Medicine, Division of Oncology, University Hospital Basel, Basel, Switzerland.

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Classifications MeSH