Cytokine profiling identifies circulating IL-2, IL23 and sPD-L1 as prognostic biomarkers for treatment outcomes in non-small cell lung cancer patients undergoing anti-PD1 therapy

Kriti Jain ¹, Anika Goel ¹, Deepa Mehra ¹

⁰Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi, India.

Frontiers in Oncology +

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July 23, 2025

View abstract on PubMed

Summary

Circulating cytokines like IL-2, IL-23, and sPD-L1 can predict treatment response and survival in advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Combined IL-2 and sPD-L1 levels offer enhanced predictive accuracy for outcomes.

Area Of Science

Oncology
Immunotherapy
Biomarker Discovery

Background

Advanced non-small cell lung cancer (NSCLC) presents significant treatment challenges.
Immune checkpoint inhibitor (ICI) therapy has revolutionized NSCLC treatment but response varies.
Predictive biomarkers are crucial for optimizing ICI therapy efficacy.

Purpose Of The Study

To investigate the predictive potential of circulating cytokines for treatment response and survival in advanced NSCLC patients.
To identify specific cytokine profiles associated with clinical response and patient outcomes.
To evaluate the utility of cytokine biomarkers in guiding personalized immunotherapy strategies.

Main Methods

A cohort of 64 advanced NSCLC patients receiving ICI therapy was analyzed.
Baseline serum samples were profiled for cytokine levels using multiplex assays.
Statistical analyses included logistic regression, Cox regression, and Kaplan-Meier survival analysis.
Quantitative real-time PCR validated key cytokine gene expression in PBMCs.

Main Results

Elevated baseline IL-2, IL-23, and soluble PD-L1 (sPD-L1) levels correlated with clinical response to ICI therapy.
sPD-L1 was an independent predictor of response (AUC = 0.87).
IL-2, sPD-L1, and IL-23 were significantly associated with progression-free survival (PFS) and overall survival (OS).
Combined IL-2 and sPD-L1 profiling significantly enhanced prediction of PFS and OS (AUC = 0.95).

Conclusions

Baseline circulating cytokine profiles, especially IL-2, sPD-L1, and IL-23, offer valuable prognostic and predictive information.
These biomarkers can aid in personalizing immunotherapy approaches for advanced NSCLC.
Cytokine profiling may guide clinical decision-making for optimizing patient outcomes with ICI therapy.

Keywords:

IL-2 IL-23 biomarkers immune checkpoint inhibitors (ICIs) nivolumab non-small cell lung cancer (NSCLC) sPD-L1