Related Experiment Video
Updated: Jan 25, 2026
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy
Sonja Althammer1, Tze Heng Tan2, Andreas Spitzmüller2
1ONE LOGIC, Munich, Germany.
Background:
Immune checkpoint therapies (ICTs) targeting the programmed cell death-1 (PD1)/programmed cell death ligand-1 (PD-L1) pathway have improved outcomes for patients with non-small cell lung cancer (NSCLC), particularly those with high PD-L1 expression. However, the predictive value of manual PD-L1 scoring is imperfect and alternative measures are needed. We report an automated image analysis solution to determine the predictive and prognostic values of the product of PD-L1+ cell and CD8+ tumor infiltrating lymphocyte (TIL) densities (CD8xPD-L1 signature) in baseline tumor biopsies.
Methods:
Archival or fresh tumor biopsies were analyzed for PD-L1 and CD8 expression by immunohistochemistry. Samples were collected from 163 patients in Study 1108/NCT01693562, a Phase 1/2 trial to evaluate durvalumab across multiple tumor types, including NSCLC, and a separate cohort of 199 non-ICT- patients. Digital images were automatically scored for PD-L1+ and CD8+ cell densities using customized algorithms applied with Developer XD™ 2.7 software.
Results:
For patients who received durvalumab, median overall survival (OS) was 21.0 months for CD8xPD-L1 signature-positive patients and 7.8 months for signature-negative patients (p = 0.00002). The CD8xPD-L1 signature provided greater stratification of OS than high densities of CD8+ cells, high densities of PD-L1+ cells, or manually assessed tumor cell PD-L1 expression ≥25%. The CD8xPD-L1 signature did not stratify OS in non-ICT patients, although a high density of CD8+ cells was associated with higher median OS (high: 67 months; low: 39.5 months, p = 0.0009) in this group.
Conclusions:
An automated CD8xPD-L1 signature may help to identify NSCLC patients with improved response to durvalumab therapy. Our data also support the prognostic value of CD8+ TILS in NSCLC patients who do not receive ICT.
Trial Registration:
ClinicalTrials.gov identifier: NCT01693562 . Study code: CD-ON-MEDI4736-1108. Interventional study (ongoing but not currently recruiting). Actual study start date: August 29, 2012. Primary completion date: June 23, 2017 (final data collection date for primary outcome measure).
Insights
An automated CD8xPD-L1 signature accurately predicts durvalumab response in non-small cell lung cancer (NSCLC) patients. This signature also shows prognostic value for CD8+ tumor infiltrating lymphocytes (TILs) in NSCLC patients not receiving immune checkpoint inhibitors.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint therapies (ICTs) targeting the programmed cell death-1 (PD1)/programmed cell death ligand-1 (PD-L1) pathway have improved outcomes in non-small cell lung cancer (NSCLC).
- Manual scoring of PD-L1 expression has limitations in predicting treatment response.
- Novel predictive and prognostic biomarkers are needed for NSCLC patients undergoing ICT.
Purpose of the Study:
- To evaluate the predictive and prognostic value of an automated CD8xPD-L1 signature in NSCLC.
- To assess the utility of this signature in patients treated with durvalumab and in a separate cohort not receiving ICT.
Main Methods:
- Tumor biopsies from 163 NSCLC patients in a durvalumab trial (Study 1108/NCT01693562) and 199 non-ICT patients were analyzed for PD-L1 and CD8 expression via immunohistochemistry.
- Customized algorithms were used for automated image analysis to quantify PD-L1+ cell and CD8+ tumor infiltrating lymphocyte (TIL) densities.
- The product of these densities, termed the CD8xPD-L1 signature, was calculated.
Main Results:
- In patients receiving durvalumab, the CD8xPD-L1 signature significantly stratified overall survival (OS), with median OS of 21.0 months for signature-positive versus 7.8 months for signature-negative patients (p=0.00002).
- The CD8xPD-L1 signature demonstrated superior stratification of OS compared to high PD-L1 expression (≥25%), high CD8+ cell density, or high PD-L1+ cell density alone.
- In non-ICT patients, the CD8xPD-L1 signature did not stratify OS, but high CD8+ TIL density was associated with improved median OS (67 months vs 39.5 months, p=0.0009).
Conclusions:
- An automated CD8xPD-L1 signature holds potential for identifying NSCLC patients likely to respond favorably to durvalumab therapy.
- The study findings support the prognostic significance of CD8+ TILs in NSCLC patients who do not receive immune checkpoint inhibitors.
More Related Videos
07:04Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
Related Concept Videos
01:26PD Controller: Design
Designing a continuous-data controller requires selecting and linking components like adders and integrators, which are fundamental in Proportional,...
02:27Predicting Molecular Geometry
01:07Time-Domain Interpretation of PD Control
Consider the example of control of motor torque. Initially, a positive...
01:03Prediction Intervals
However, the point estimate is most likely not the exact value of the population parameter, but close to it. After calculating point estimates, we construct interval estimates, called confidence intervals or prediction intervals. This prediction interval comprises a range of values unlike the point estimate and is a better predictor of the observed sample value, y.
01:24Frequency-Domain Interpretation of PD Control
The proportional control gain, combined with the...
00:59Gene Therapy