Gut microbial structural variation associates with immune checkpoint inhibitor response
Open accessAbstract
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts’ prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
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Liu et al. identified highly variable structural variations in microbial genomes associated with ICI treatment outcomes in patients with renal cell carcinoma, NSCLC, and melanoma.
“For instance, Liu et al. using metagenomic sequencing, identified highly variable structural variations in microbial genomes, which were associated with ICI treatment outcomes in patients with renal cell carcinoma, non-small cell lung cancer (NSCLC), and melanoma144.”
From Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors (2025) · cites this paper as [144]
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Cites
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Sorted by citations
Andreu-Sánchez, S., Blanco-Míguez, A., Wang, D., Golzato, D., Manghi, P., Heidrich, V., Fackelmann, G., Zhernakova, D. V., Kurilshikov, A., Valles-Colomer, M., et al. (2025) · Cell · doi:10.1016/j.cell.2025.04.014 · Cited by 81 · see citing works
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Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors
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“Forinstance,Liuetal.using metagenomicsequencing,identi fi ed highly variable structural variations in microbial genomes, which were associated with ICI treatment outcomes in patients with renal cell carcinoma, non-small cell lung cancer (NSCLC), and melanoma 144 .”
- Authors
- Liu, R., Zou, Y., Wang, W.-Q., Chen, J.-H., Zhang, L., Feng, J., Yin, J.-Y., Mao, X.-Y., Li, Q., Luo, Z.-Y., Zhang, W., & Wang, D.-M.
- Affiliations
- Central South University (CN)
- Corresponding author
- Liu, Rong
- Zhang, Wei
- Venue
- Nature Communications
- Published
- 2023-11-16
- Volume
- 14
- Issue
- 1
- Pages
- 7421-7421
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10654443
- OpenAlex
- W4388734849
- Cited by
- 45
- References
- 16
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 14
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Central South University
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.222.016)
- Xiangya Hospital, Central South University
- National Key Research and Development Program of China (2021YFA1301200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, immune checkpoint inhibitors, structural variants, immune-related adverse events, Akkermansia muciniphila, Dorea formicigenerans, Bacteroides caccae, glucose metabolism genes, progression-free survival, overall survival
- MeSH terms
- Gastrointestinal Microbiome, Immune Checkpoint Inhibitors, Bacteria, Humans, Neoplasms, Metagenome, Microbiota
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