Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity
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Abstract
Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8 + T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.
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ICB appears to promote bacterial translocation from the gut to lymphoid organs via dendritic cells, suggesting that bacteria could disseminate to distant tumors and boost antitumor immunity.
“Additionally, ICB appears to promote bacterial translocation from the gut to lymphoid organs via dendritic cells (Choi et al., 2023), suggesting that bacteria—possibly mobilized by ICB-induced toxicities (Almonte et al., 2021)—could disseminate to distant tumors and boost antitumor immunity.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Choi et al., 2023
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- Authors
- Choi, Y., Lichterman, J. N., Coughlin, L. A., Poulides, N., Li, W., Del Valle, P., Palmer, S. N., Gan, S., Kim, J., Zhan, X., Gao, Y., Evers, B. M., Hooper, L. V., Pasare, C., & Koh, A. Y.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Division of Hematology/Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Howard Hughes Medical Institute (US)
- Cincinnati Children's Hospital Medical Center (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Corresponding author
- Koh, Andrew Y.
- ORCID
- Venue
- Science Immunology
- Published
- 2023-03-31
- Volume
- 8
- Issue
- 81
- Pages
- eabo2003-eabo2003
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC10080670
- OpenAlex
- W4323031394
- Cited by
- 132
- References
- 90
- Citations by year
- 2026: 35 · 2025: 47 · 2024: 34 · 2023: 16
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- University of Texas Southwestern Medical Center
- National Institutes of Health (5t32ai005284-45, 5T32AI005284)
- National Cancer Institute (R01CA231303)
- National Institute of Allergy and Infectious Diseases (T32-AI005284, R01AI123163, 5-T32-AI005284, AI123176, 5T32AI005284-43, K24AI150992, R01AI155426, R01AI123176)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070855)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immune checkpoint blockade, gut microbiota, bacterial translocation, melanoma, dendritic cell activation, tumor-draining lymph nodes, CD8+ T cells, antibiotic therapy, mesenteric lymph nodes, cancer immunotherapy
- MeSH terms
- Gastrointestinal Microbiome, Immune Checkpoint Inhibitors, Humans, Lymph Nodes, Melanoma, CD8-Positive T-Lymphocytes
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