title: Prognostic impact of the expression of NCR1 and NCR3 NK cell receptors and PD-L1 on advanced non-small cell lung cancer.
abstract: The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantifiedNCR1(which codes for NKp46) andNCR3(which codes for NKp30), as well as that of threeNCR3splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C). NSCLC patients expressed lower levels ofNCR1than did HV. Remarkably,NCR3was lower in NSCLC patients than in HV as well as in all other malignancies. Moreover, a discrete proportion of NSCLC patients exhibited a particular low ratio between NKp30B and NKp30C (ΔBC). In the overall cohort, low expression ofNCR3correlated with poor overall and progression-free survival (PFS). When patients were stratified according to the level of PD-L1 expression by NSCLC cells, within the PD-L1highcategory (>5% positive tumors), the sole parameter that affected prognosis was the expression ofNCR1. However, in patients bearing tumors with negative PD-L1 expression on tumor or tumor-infiltrating stromal cells, the ΔBClowpatients exhibited a dismal prognosis. Altogether, these results strongly suggest that NK cells mediate immunosurveillance against NSCLC and that measuring NK cell receptor expression by blood cells can yield useful biomarkers for patient stratification.
authors.affiliation: Transgene S.A, Parc d'innovation, Illkirch-Graffenstaden Cedex, France; Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Fend
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT), GRCC, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; Department of Pathology, GRCC, Villejuif, France; INSERM, GRCC, Villejuif, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Adam
authors.affiliation: Transgene S.A, Parc d'innovation , Illkirch-Graffenstaden Cedex, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Bastien
authors.affiliation: INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Caignard
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Messaoudene
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; INSERM, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Iribarren
authors.affiliation: Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; INSERM, Center de Recherche des Cordeliers, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France; Drug Development Department (DITEP), GRCC, Villejuif, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: INSERM, Unité Mixte de Recherche, University of Franche-Comté, Besançon, France; Etablissement Français du Sang de Bourgogne Franche-Comté, Besançon, France; Université de Franche-Comté, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Department of Pediatric Oncology, GRCC, Villejuif, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Transgene S.A, Parc d'innovation , Illkirch-Graffenstaden Cedex, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Barraud
authors.affiliation: Transgene S.A, Parc d'innovation , Illkirch-Graffenstaden Cedex, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Limacher
authors.affiliation: Gustave Roussy Cancer Campus (GRCC) , Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; INSERM, Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Metabolomics and Cell Biology Platforms, GRCC, Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, GRCC, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT), GRCC, Villejuif, France; University of Paris Sud XI, Kremlin Bicêtre, France; Department of Immuno-Oncology, GRCC, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
keywords: Biomarker; NK cells; NKp30; NKp46; NSCLC; PD-L1