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Sex-specific cytokine signatures as predictors of anti-PD1 therapy response in non-small cell lung cancer

  • 0Atlantic Cancer Research Institute, Moncton, NB, Canada.
Frontiers in Immunology +

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July 1, 2025

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July 1, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cytokine profiling in non-small cell lung cancer (NSCLC) patients receiving anti-PD1 therapy reveals potential biomarkers for treatment response. Sex-specific differences in cytokine correlations highlight the importance of considering gender in immuno-oncology biomarker studies.

Area Of Science

  • Immuno-oncology
  • Biomarker Discovery
  • Oncology

Background

  • Immune checkpoint inhibitors (ICI) have improved non-small cell lung cancer (NSCLC) treatment outcomes.
  • However, over half of NSCLC patients do not achieve durable responses to ICI therapy.
  • Identifying circulating biomarkers is crucial for stratifying patients and predicting response to ICI.

Purpose Of The Study

  • To profile circulating cytokines and chemokines in NSCLC patients undergoing anti-PD1 therapy.
  • To correlate cytokine levels with treatment response, progression-free survival (PFS), and overall survival (OS).
  • To investigate potential sex disparities in these correlations.

Main Methods

  • Twenty-four cytokines and chemokines were measured in NSCLC patient plasma before and during anti-PD1 treatment.
  • Correlations between cytokine levels and treatment response, PFS, and OS were analyzed.
  • Sex-specific differences in these correlations were investigated using statistical analyses and UMAP/k-means clustering.

Main Results

  • Baseline CCL5 levels correlated with anti-PD1 response regardless of sex.
  • CXCL5 and CXCL10 showed sex-specific associations with response (males and females, respectively).
  • VEGF and CD40L correlated with shorter PFS/OS, while CCL5 and CXCL5 correlated with longer PFS/OS. Significant sex disparities were observed for CCL5, CXCL10, and VEGF in predicting response and survival.

Conclusions

  • Plasma cytokine levels serve as potential biomarkers for predicting anti-PD1 therapy response in NSCLC.
  • Sex is a critical variable that influences the correlation between cytokines and treatment outcomes in immuno-oncology.
  • Further research considering sex differences is warranted for developing robust biomarker strategies in NSCLC treatment.

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