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

Jean-David Fumet; Corentin Richard; Fanny Ledys; Quentin Klopfenstein; Philippe Joubert; Bertrand Routy; Caroline Truntzer; Andréanne Gagné; Marc-André Hamel; Camila Figueiredo Guimaraes; Bruno Coudert; Laure Arnould; Laure Favier; Aurélie Lagrange; Sylvain Ladoire; Pierre Saintigny; Sandra Ortiz-Cuaran; Maurice Perol; Pascal Foucher; Paul Hofman; Marius Ilie; Sandy Chevrier; Romain Boidot; Valentin Derangère; François Ghiringhelli

doi:10.1038/s41416-018-0220-9

Article dans une revue

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

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio] / Cancer

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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01980112
Contributeur : Lnc - Université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : lundi 14 janvier 2019 - 11:00:48
Dernière modification le : mardi 4 janvier 2022 - 03:49:01

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

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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

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