Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer
Open accessAbstract
Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade immune detection. Although ICIs have shown promising results, especially in solid tumors, patient responses vary widely due to multiple intrinsic and extrinsic factors within the tumor microenvironment. Emerging evidence suggests that the gut microbiota plays a pivotal role in modulating immune responses at the tumor site and may even influence treatment outcomes in cancer patients receiving ICIs. This review explores the complex interactions between the gut microbiota and the tumor microenvironment, examining how these interactions could impact the effectiveness of ICI therapy. Furthermore, we discuss how dysbiosis, an imbalance in gut microbiota composition, may contribute to resistance to ICIs, and highlight microbiota-targeted strategies to potentially overcome this challenge. Additionally, we review recent studies investigating the diagnostic potential of microbiota profiles in cancer patients, considering how microbial markers might aid in early detection and stratification of patient responses to ICIs. By integrating insights from recent preclinical and clinical studies, we aim to shed light on the potential of microbiome modulation as an adjunct to cancer immunotherapy and as a diagnostic tool, paving the way for personalized therapeutic approaches that optimize patient outcomes.
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Interactions between gut microbes and the tumor microenvironment are dynamic and bidirectional and influence recruitment and functional programming of immune cells within tumors.
“The interactions between gut microbes and the TME are highly dynamic and bidirectional, which influence both the recruitment and functional programming of immune cells within tumors [44]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [44]
The sections “Influence on Lymphocyte Relocation and Immunotherapy Efficacy” and “Translocation and Immune Cell Recruitment in the TME” describe microbial effects on immune-cell movement into tumors and CD8+ T-cell differentiation. “Avoiding Immune Destruction” also says gut microbiota influence immune-cell differentiation and shape the tumor microenvironment. The passages support these effects but do not establish that the gut microbiota–tumor microenvironment interaction itself is bidirectional; no page numbers were provided. (LLM, conf=0.82)
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Microbiota and the Immune System—Actors in the Gastric Cancer Story
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Microbiota and Extracellular Vesicles in Anti-PD-1/PD-L1 Therapy
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Rahimi, A. R., Baghernejadan, Z., Hazrati, A., Malekpour, K., Samimi, L. N., Najafi, A., Falak, R., & Khorramdelazad, H. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118014 · Cited by 39 · see citing works
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Self-citationRecent research progress and clinical status of immunotherapy for colorectal cancer
Huo, Z., Liu, G., & Li, J. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.06.089 · Cited by 23 · see citing works
A Comprehensive Oncological Biomarker Framework Guiding Precision Medicine
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The Gut–Brain Axis in Brain Tumors: Insights into Tumor Development, Progression, and Therapy
Scuderi, S. A., Ardizzone, A., Calcaterra, E., Palermo, N., Luca, F. D., Catalfamo, A., Esposito, E., & Capra, A. P. (2025) · Biomedicines · doi:10.3390/biomedicines13092172 · Cited by 10 · see citing works
Abdalla, W., Ibrahim, W. N., Abdallah, A. M., Al‐Asmakh, M., & Said, S. S. (2025) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.70070 · Cited by 9 · see citing works
Self-citationThe tumor ecosystem: Rewiring an open, systemically integrated network for therapeutic gain
Chiodelli, P., Papait, A., Agoni, L., Quaglia, F., Silini, A. R., & Parolini, O. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119047 · Cited by 10 · see citing works
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Phage therapy in oncology: opportunities for cancer prevention and treatment
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Snake venom in conjugation with silica nanoparticles: an emerging cancer therapy
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From Dysbiosis to Symbiosis: Using the Gut Microbiome to Improve Cancer Outcomes
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- Authors
- Said, S., & Ibrahim, W.
- Affiliations
- Qatar University (QA)
- Corresponding author
- Ibrahim, Wisam
- Venue
- Cancer Management and Research
- Publisher
- Informa UK Limited
- Published
- 2025-01
- Volume
- Volume 17
- Pages
- 171-192
- ISSN
- 1179-1322 (ISSN-L)
- PMC
- PMC11776928
- OpenAlex
- W4406825487
- Cited by
- 25
- References
- 146
- Citations by year
- 2026: 15 · 2025: 10
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Management and Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Qatar University QSpace (Qatar University) (submittedVersion)
- Funders
- Qatar University
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- gut microbiota, tumor microenvironment, immune checkpoint inhibitors, cancer immunotherapy, dysbiosis, immune checkpoint inhibitor resistance, microbiota-targeted therapy, microbial biomarkers, cancer diagnosis, precision oncology, tumor immune evasion
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