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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 cancerResearch in context
- Source :
- EBioMedicine, Vol 92, Iss , Pp 104633- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Summary: 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
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 92
- Issue :
- 104633-
- Database :
- Directory of Open Access Journals
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f4bad0461854aff8dc0c5518a34fcbc
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.ebiom.2023.104633