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Br J Cancer. 2018 Oct;119(8):950-960. doi: 10.1038/s41416-018-0220-9. Epub 2018 Oct 15.

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

Author information

1
Department of Medical Oncology, Center GF Leclerc, Dijon, France.
2
Research Platform in Biological Oncology, Dijon, France.
3
GIMI Genetic and Immunology Medical Institute, Dijon, France.
4
University of Burgundy-Franche Comté, Dijon, France.
5
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, QC, Canada.
6
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
7
Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada.
8
Department of Pathology, Center GF Leclerc, Dijon, France.
9
Department of Medical Oncology, Center Leon Berard, Lyon, France.
10
Department of Thoracic Oncology, Dijon University Hospital, Dijon, France.
11
Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Nice University Hospital, Université Côte d'Azur, Nice, France.
12
Hospital-Integrated Biobank (BB-0033-00025), FHU OncoAge, Nice University Hospital, Université Côte d'Azur, Nice, France.
13
Department of Medical Oncology, Center GF Leclerc, Dijon, France. fghiringhelli@cgfl.fr.
14
Research Platform in Biological Oncology, Dijon, France. fghiringhelli@cgfl.fr.
15
GIMI Genetic and Immunology Medical Institute, Dijon, France. fghiringhelli@cgfl.fr.
16
University of Burgundy-Franche Comté, Dijon, France. fghiringhelli@cgfl.fr.
17
INSERM UMR1231, Dijon, France. fghiringhelli@cgfl.fr.

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.

PMID:
30318514
PMCID:
PMC6203820
DOI:
10.1038/s41416-018-0220-9
[Indexed for MEDLINE]
Free PMC Article

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