Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response
Open accessAbstract
Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri , and disproportional enrichment of circulating exhaustive CD8 + T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.
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The gut microbiota influences systemic and tumor immunity.
“This complex community of microorganisms—including bacteria, archaea, eukaryotes, fungi, and viruses—lives in the gastrointestinal tract (Donaldson et al., 2016) and influences systemic and tumor immunity (Derosa et al., 2022; Kim et al., 2023).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Kim et al., 2023
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- Authors
- Kim, C. G., Koh, J.-Y., Shin, S.-J., Shin, J.-H., Hong, M., Chung, H. C., Rha, S. Y., Kim, H. S., Lee, C.-K., Lee, J. H., Han, Y., Kim, H., Che, X., Yun, U.-J., Kim, H., Kim, J. H., Lee, S. Y., Park, S. K., Park, S., Kim, H., Ahn, J. Y., Jeung, H.-C., Lee, J. S., Nam, Y.-D., & Jung, M.
- Affiliations
- Yonsei University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Korea Food Research Institute (KR)
- Corresponding author
- Jeung, Hei-Cheul
- Lee, Jeong Seok
- Nam, Young-Do
- Jung, Minkyu
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 4
- Issue
- 11
- Pages
- 101251
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC10694627
- OpenAlex
- W4387996822
- Cited by
- 45
- References
- 61
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 9
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (2021R1A2C2009400, 2021R1I1A1A01059271, 2022R1C1C1012634)
- Yonsei University College of Medicine (6-2020-0231)
- Ministry of Science, ICT and Future Planning (E0170600-06)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- advanced gastric cancer, PD-1 inhibitors, immune checkpoint blockade, gut microbiota, Lactobacillus gasseri, CD8+ T cells, exhaustion, progression-free survival, overall survival, irinotecan
- MeSH terms
- Gastrointestinal Microbiome, Immune Checkpoint Inhibitors, Anti-Bacterial Agents, Humans, Stomach Neoplasms, CD8-Positive T-Lymphocytes, Programmed Cell Death 1 Receptor
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