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Prognostic and predictive role of CD8 and PD-L1 determination in lung tumor tissue of patients under anti-PD-1 therapy

Jean-David Fumet 1, 2, 3, 4 Corentin Richard 2, 3, 4 Fanny Ledys 2, 3, 4 Quentin Klopfenstein 2, 3 Philippe Joubert 5 Bertrand Routy 6 Caroline Truntzer 2, 3 Andréanne Gagné 5 Marc-André Hamel 5 Camila Figueiredo Guimaraes 6 Bruno Coudert 1 Laure Arnould 7 Laure Favier 1 Aurélie Lagrange 1 Sylvain Ladoire 1, 4 Pierre Saintigny 8 Sandra Ortiz-Cuaran 8 Maurice Perol 8 Pascal Foucher 9, 10 Paul Hofman 11, 12 Marius Ilie 11, 12 Sandy Chevrier 2, 3 Romain Boidot 2, 3 Valentin Derangère 2, 3 François Ghiringhelli 1, 2, 3, 4, 13, *
* Auteur correspondant
1 Département d'oncologie médicale [Centre Georges-François Leclerc]
2 Plateforme de transfert en biologie cancérologique [Dijon]
CEP - Centre d'épidémiologie des populations, UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
3 GIMI - Genetic and Immunology Medical Institute
4 UBFC - Université Bourgogne Franche-Comté [COMUE]
5 IUCPQ - Institut Universitaire de Cardiologie et de Pneumologie de Québec
6 CHUM - Centre Hospitalier de l'Université de Montréal
7 Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc]
8 Service d'oncologie médicale (Centre Léon Bérard)
9 TRACES - Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés
10 Férération d'oncologie thoracique (CHU de Dijon)
11 Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice]
12 Hospital-Integrated Tumor Biobank [Hôpital Pasteur, Sophia Antipolis]
13 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
Abstract : Background No study has evaluated the predictive and prognostic role of CD8 and PD-L1 coexpression in non–small-cell lung cancer (NSCLC). Methods We analyzed RNA sequencing and/or immunohistochemistry staining in NSCLC patients from The Cancer Genome Atlas (n = 1016), and 34 metastatic NSCLC samples not treated by immunotherapy as prognostic cohorts. As predictive aspect of CD8 and PD-L1, we used 85 NSCLC patients treated with anti-PD-1. Two validation cohorts were used including 44 NSCLC patients treated with anti-PD-1 and an external cohort with different tumor types. Results In prognostic cohorts, high CD8A expression was associated with longer OS (p = 0.02), while high CD274 mRNA was associated with poor prognosis (p = 0.05). In predictive cohort, high CD8 expression and CD8A mRNA were associated with longer progression-free survival (PFS) (p = 0.0002). There was no significant association between PD-L1 expression and PFS while high CD274 mRNA was associated with longer PFS (p = 0.009). A combination of CD8A and CD274 was highly predictive of outcome. These results were confirmed in the validation cohorts. This two-genes signature demonstrated similar results compared to gold standard signatures. Conclusion CD8 represents both a prognostic and predictive factor of outcomes, while PD-L1 share different prognostic and predictive roles.
Keywords : CD8 Lung tumor tissue
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01980112
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : lundi 14 janvier 2019 - 11:00:48
Dernière modification le : mercredi 5 août 2020 - 03:11:03

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UNIV-BOURGOGNE | LNC-CADIR | CNRS | EHESS | TRACES | CGFL | FNCLCC | UNIV-TLSE2 | LNC-UMR866 | PSL

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Jean-David Fumet, Corentin Richard, Fanny Ledys, Quentin Klopfenstein, Philippe Joubert, et al.. Prognostic and predictive role of CD8 and PD-L1 determination in lung tumor tissue of patients under anti-PD-1 therapy. British Journal of Cancer, Cancer Research UK, 2018, 119 (8), pp.950-960. ⟨10.1038/s41416-018-0220-9⟩. ⟨hal-01980112⟩

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