Integrative stratification of response to immunotherapy using host and microbial signatures in patients with advanced non-small cell lung cancer.
6 affiliations
- 1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
- 2CJ Bioscience, Inc., 7th Floor, Grand Central B, 14 Sejong-Daero, Jung-Gu, Seoul, 04527, Republic of Korea.
- 3Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
- 4Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
- 5CJ Bioscience, Inc., 7th Floor, Grand Central B, 14 Sejong-Daero, Jung-Gu, Seoul, 04527, Republic of Korea. [email protected].
- 6Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea. [email protected].
Abstract
Background
The gut microbiome has been linked to responses to immune checkpoint inhibitors (ICIs), yet longitudinal multi-omics studies remain limited.Methods
Here, we serially collected gut microbiome data and performed multi-omics analyses, including RNA sequencing (RNA-seq) and whole-exome sequencing (WES), on samples from 92 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, to identify factors contributing to treatment response. We compared gut microbiome data with those of a healthy cohort (n = 92) and examined changes in gut microbial signatures during immunotherapy. Gut microbiome data from publicly available ICI-treated cohorts (n = 728) were also used together with our own cohort to develop and validate a score for classifying response to ICIs.Results
Responders (defined as complete response, partial response, or stable disease of at least 6 months) were enriched for Faecalibacterium, while non-responders were enriched for Lactobacillus and Escherichia, with these taxa showing specific associations with dietary fiber intake and antibiotic use. Dynamic shifts in dysbiotic signatures were observed throughout treatment and disease progression, with dissimilarity from the healthy cohort decreasing after treatment only in responders but increasing at progression in both responders and non-responders. We also developed a cross-population score based on the ratio of responder- to non-responder-associated microbial markers. This score showed a significant positive correlation with the index reflecting gut microbial health status and improved response stratification when combined with tumor mutational burden (TMB).Conclusions
These findings highlight the importance of characterizing dysbiosis using gut microbial signatures, which act along a distinct and complementary axis to explain responses to ICIs.
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BibTeX
@article{lee2026integrative,
title = {{Integrative stratification of response to immunotherapy using host and microbial signatures in patients with advanced non-small cell lung cancer.}},
author = {Jii Bum Lee and Junwon Yang and Mauricio Chalita and Yeonjae Jung and Haangik Park and Myungja Ro and Hyun Kim and Eunchong Yang and Soeun Choi and Minyoung Kim and Arim Min and Bo-Eun Kwon and Jieun Im and Hyunjeong Kim and Hyunkyung Park and Sun Min Lim and Min Hee Hong and Sein Park and Yeong Ouk Kim and Jongsik Chun and Hyun-Seok Oh and Byoung Chul Cho},
journal = {Genome medicine},
year = {2026},
month = aug,
doi = {10.1186/s13073-026-01736-5},
url = {https://europepmc.org/article/MED/42972584},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrative stratification of response to immunotherapy using host and microbial signatures in patients with advanced non-small cell lung cancer.
AU - Jii Bum Lee
AU - Junwon Yang
AU - Mauricio Chalita
AU - Yeonjae Jung
AU - Haangik Park
AU - Myungja Ro
AU - Hyun Kim
AU - Eunchong Yang
AU - Soeun Choi
AU - Minyoung Kim
AU - Arim Min
AU - Bo-Eun Kwon
AU - Jieun Im
AU - Hyunjeong Kim
AU - Hyunkyung Park
AU - Sun Min Lim
AU - Min Hee Hong
AU - Sein Park
AU - Yeong Ouk Kim
AU - Jongsik Chun
AU - Hyun-Seok Oh
AU - Byoung Chul Cho
PY - 2026
DA - 2026/08/06
JO - Genome medicine
DO - 10.1186/s13073-026-01736-5
UR - https://europepmc.org/article/MED/42972584
AB - Background The gut microbiome has been linked to responses to immune checkpoint inhibitors (ICIs), yet longitudinal multi-omics studies remain limited.Methods Here, we serially collected gut microbiome data and performed multi-omics analyses, including RNA sequencing (RNA-seq) and whole-exome sequencing (WES), on samples from 92 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, to identify factors contributing to treatment response. We compared gut microbiome data with those of a healthy cohort (n = 92) and examined changes in gut microbial signatures during immunotherapy. Gut microbiome data from publicly available ICI-treated cohorts (n = 728) were also used together with our own cohort to develop and validate a score for classifying response to ICIs.Results Responders (defined as complete response, partial response, or stable disease of at least 6 months) were enriched for Faecalibacterium, while non-responders were enriched for Lactobacillus and Escherichia, with these taxa showing specific associations with dietary fiber intake and antibiotic use. Dynamic shifts in dysbiotic signatures were observed throughout treatment and disease progression, with dissimilarity from the healthy cohort decreasing after treatment only in responders but increasing at progression in both responders and non-responders. We also developed a cross-population score based on the ratio of responder- to non-responder-associated microbial markers. This score showed a significant positive correlation with the index reflecting gut microbial health status and improved response stratification when combined with tumor mutational burden (TMB).Conclusions These findings highlight the importance of characterizing dysbiosis using gut microbial signatures, which act along a distinct and complementary axis to explain responses to ICIs.
SN - 1756-994X
ER -