Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EBioMedicine Année : 2023

Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer

François Ghiringhelli
  • Fonction : Auteur
Frederic Bibeau
  • Fonction : Auteur
Jean-David Fumet
  • Fonction : Auteur
Alis Ilie
  • Fonction : Auteur
Florence Monville
  • Fonction : Auteur
Caroline Laugé
  • Fonction : Auteur
Aurélie Catteau
  • Fonction : Auteur
Isabelle Boquet
  • Fonction : Auteur
Youssef Oulkhouir
  • Fonction : Auteur
Nicolas Brandone
  • Fonction : Auteur
Julien Adam
  • Fonction : Auteur
Thomas Sbarrato
Alboukadel Kassambara
  • Fonction : Auteur
Jacques Fieschi
  • Fonction : Auteur
Stéphane Garcia
  • Fonction : Auteur
Anne Laure Lepage
  • Fonction : Auteur
Pascale Tomasini
  • Fonction : Auteur

Résumé

Background Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non- small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. Methods Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routine single FFPE-slides, and the duplex-immunohistochemistry CD8 and PD-L1 staining was quantified using digital-pathology. Analytical validation was performed on two independent cohorts of 206 NSCLC patients. Quantitative parameters related to cell location, number, proximity and clustering were analysed. The Immunoscore-IC was applied on a first cohort of metastatic NSCLC patients (n = 133), treated with anti-PD1 or anti-PD-L1 mAbs. Another independent cohort (n = 132) served as validation. Findings Anti-PDL1 clone (HDX3) has similar characteristics as anti-PD-L1 clones (22C3, SP263). Densities of PD-L1+ cells, CD8+ cells and distances between CD8+ and PD-L1+ cells were quantified and the Immunoscore-IC classification was computed. Using univariate Cox model, 5 histological dichotomised variables (CD8 free of PD-L1+ cells, CD8 clusters, CD8 cells in proximity of PD-L1 cells, CD8 density and PD-L1 cells in proximity of CD8 cells) were significantly associated with Progression-Free Survival (PFS) (all P < 0.0001). Immunoscore-IC classification improved the discriminating power of prognostic model, which included clinical variables and pathologist PD-L1 assessment. In two categories, the Immunoscore-IC risk-score was significantly associated with patients’ PFS (HR = 0.39, 95% CI (0.26–0.59), P < 0.0001) and Overall Survival (OS) (HR = 0.42, 95% CI (0.27–0.65), P < 0.0001) in the training-set. Further increased hazard ratios (HR) were found when stratifying patients into three-category Immunoscore-IC (IS-IC). All patients with Low-IS-IC progressed in less than 18 months, whereas PFS at 36 months were 34% and 33% of High-IS-IC patients in the training and validation sets, respectively. Interpretation Immunoscore-IC is a powerful tool to predict the efficacy of immune-checkpoint inhibitors (ICIs) in patients with NSCLC.

Domaines

Cancer

Dates et versions

hal-04390243 , version 1 (12-01-2024)

Identifiants

Citer

François Ghiringhelli, Frederic Bibeau, Laurent Greillier, Jean-David Fumet, Alis Ilie, et al.. Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer. EBioMedicine, 2023, 92, pp.104633. ⟨10.1016/j.ebiom.2023.104633⟩. ⟨hal-04390243⟩
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