Evaluating the significance of combining PD-L1 and TILs as biomarkers in non-small cell lung cancer patients treated with immunotherapy: a systematic review

Y Derraze ¹, S M S Hashemi ², E B Ulas ²

⁰Amsterdam UMC location VUMC, Department of Pulmonary Medicine, De Boelelaan, Amsterdam, The Netherlands. y.derraze@amsterdamumc.nl.

Bjc Reports +

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September 22, 2025

View abstract on PubMed

Summary

Combining programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) shows stronger prediction for progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). This combined approach offers improved prognostic value over individual biomarkers.

Area Of Science

Oncology
Immunology
Biomarker Research

Background

Programmed death-ligand 1 (PD-L1) expression is a biomarker for immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC), but its predictive power is suboptimal.
Tumor-infiltrating lymphocytes (TILs), especially CD8+ T cells, are emerging as potential complementary biomarkers in NSCLC.
The combined predictive value of PD-L1 and TILs for ICI treatment outcomes in NSCLC remains incompletely understood.

Purpose Of The Study

To systematically evaluate the predictive value of programmed death-ligand 1 (PD-L1) expression and CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs).
To assess the combined effect of PD-L1 and TILs on progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIs.

Main Methods

Systematic literature search conducted across Ovid/Medline, Embase, and Web of Science databases.
Included studies focused on NSCLC patients treated with ICIs, analyzing PD-L1 expression and CD8+ TILs.
Primary outcomes analyzed were progression-free survival (PFS) and overall survival (OS); secondary outcomes included objective response rate (ORR) and durable clinical benefit (DCB). Study quality was assessed using the Newcastle-Ottawa Scale.

Main Results

Thirteen studies comprising 2490 patients were included in the meta-analysis.
PD-L1 expression alone was associated with improved PFS (HR: 0.67) but not significantly with OS.
TILs alone did not show significant predictive value for PFS or OS. However, the combination of PD-L1 and TILs demonstrated the strongest predictive value for both PFS (HR: 0.39) and OS (HR: 0.42).

Conclusions

The combined assessment of PD-L1 expression and CD8+ TILs offers superior predictive value for progression-free survival and overall survival in NSCLC patients undergoing ICI therapy compared to either biomarker alone.
Integrating both PD-L1 and TILs into predictive models may enhance patient selection for immune checkpoint inhibitors, although clinical implementation requires further consideration.
Further research is warranted to optimize the clinical application of combined PD-L1 and TILs biomarkers in NSCLC treatment strategies.

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