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, Bruno Coudert, Laurent 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 Derangere and François Ghiringhelli.

Abstract:

Background: No study has evaluated the predictive and prognostic role of CD8 and PD-L1 co-expression in non-small cell lung cancer (NSCLC).

Methods: We analyzed RNA sequencing and/or IHC staining in NSCLC patients from The Cancer Genome Atlas (n=353) 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 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 2-genes signature demonstrated similar results compared to gold standard signatures.

Conclusions: CD8 represents both a prognostic and predictive factor of outcomes, while PD-L1 share different prognostic and predictive role.