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Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer. | LitMetric

AI Article Synopsis

  • This study explores the differences in how patients with non-small cell lung cancer (NSCLC) respond to immune checkpoint inhibitors (ICIs) and seeks to identify key biomarkers that predict these responses.
  • Researchers analyzed samples from 33 lung cancer biopsies, focusing on 14 taken before ICI treatment, and found that non-responders had more regulatory and memory T cells, while responders displayed diverse activated CD8+ T cells.
  • They identified specific tumor cell activity linked to resistance to ICIs, achieving over 95% accuracy in predicting patient responses by combining immune cell profiles with tumor characteristics, highlighting the importance of the tumor-immune environment in NSCLC treatment.

Article Abstract

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICIs). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (area under the curve [AUC]) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548875PMC
http://dx.doi.org/10.7554/eLife.98366DOI Listing

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