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

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

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 infl...

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Main Authors: Nayoung Kim, Sehhoon Park, Areum Jo, Hye Hyeon Eum, Hong Kwan Kim, Kyungjong Lee, Jong Ho Cho, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Jung-Il Lee, Jung Won Choi, Dasom Jeong, Minsu Na, Huiram Kang, Jeong Yeon Kim, Jung Kyoon Choi, Hae-Ock Lee, Myung-Ju Ahn
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2024-11-01
Series:eLife
Subjects:
non-small cell lung cancer
immune checkpoint therapy
late-stage biopsy
single-cell RNA sequencing
response signature
Online Access:https://elifesciences.org/articles/98366
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Summary: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.
ISSN:2050-084X

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