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Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients
Open accessAbstract
The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05–2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49–2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.
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“However, increasing clinical evidence suggests that systemic antibiotics abolish immune checkpoint blockade efficacy and decrease patient survival (133, 136, 137).”
From The microbiome and human cancer (2021) · cites this paper as [136]
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BackgroundInfluential
Cited by
Sorted by citations
The microbiome and human cancer
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Antibiotic use influences outcomes in advanced pancreatic adenocarcinoma patients
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“conducted a dedicated meta-analysis to pool all data from 19 relevant publications comprising a total of 2,740 cancer patients.(77) Statistically significant reduction in PFS and overall survival were observed when comparing blockade-treated patients with the use of antibiotics to those without regardless of the cance…”
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ResultThe role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer
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“Retrospective clinical data suggests that antibiotic use prior to ICPI can reduce the effectiveness of these agents, likely through altered composition of the gut microbiome (5).”
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Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy
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BackgroundIntratumour microbiome of pancreatic cancer
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“Clinical evidence has shown that antibiotic treatment reduces the efficacy of immune checkpoint inhibitors and patient survival rates [210, 211].”
BackgroundKaramanolis, N. N., Kounatidis, D. C., Vallianou, N. G., Dimitriou, K., Tsaroucha, E., Tsioulos, G., Anastasiou, I. A., Mavrothalassitis, E., Karampela, Ι., & Dalamaga, Μ. (2024) · Antibiotics · doi:10.3390/antibiotics14010009 · Cited by 28
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Gut Bacteria—Not for the Faint of Heart
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Intratumor microbiota: a novel tumor component
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“There is also clinical evidence that systemic antibiotics abolish the effects of immune checkpoint blockade and reduce patient survival (Derosa et al. 2018; Huang et al. 2019; Pinato et al. 2019).”
BackgroundSelf-citationAntibiotic Resistance Risk with Oral Tetracycline Treatment of Acne Vulgaris
Swallow, M. A., Fan, R., Cohen, J. M., & Bunick, C. G. (2022) · Antibiotics · doi:10.3390/antibiotics11081032 · Cited by 23
The Gut Microbiome and Pancreatic Cancer Development and Treatment
Attebury, H., & Daley, D. (2023) · The Cancer Journal · doi:10.1097/ppo.0000000000000647 · Cited by 24
Antibiotics, cancer risk and oncologic treatment efficacy: a practical review of the literature
Lopes, M. S. M., Machado, L. M., Silva, P. A. I. A., Uchiyama, A. A. T., Yen, C. T., Ricardo, E. D., Mutão, T. S., Pimento, J. R., Shimba, D. S., Hanriot, R. D. M., et al. (2020) · ecancermedicalscience · doi:10.3332/ecancer.2020.1106 · Cited by 25
“Subgroup analysis on the type of ICI revealed a negative impact on all drugs and combinations [68].”
BackgroundDivergent tumor immunity determined by bacteria-cancer cell engagement
Yao, B., Liu, X.-M., Ruan, K., Fang, X., Jiang, C., Bian, W., Guo, Y., Zhu, X., Shang, Z., Hu, T., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.044 · Cited by 25
The cure from within? a review of the microbiome and diet in melanoma
Kumar, P. R., Brazel, D., DeRogatis, J. M., Goldstein, J. B., Whiteson, K., Chow, W. A., Tinoco, R., & Moyers, J. T. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10029-3 · Cited by 22
“26); however, patient level factors were not controlled for in this analysis[69].”
BackgroundZapata, M. E. S., Pellitero, A. M., Isla, D., Gálvez, E. H., Ruiz, M. G., Sesma, A., Barbero-Herranz, R., Galeano, J., del Campo, R., Ocáriz, M., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e33684 · Cited by 20
“In view of this discrepancy in response, attempts have been made to identify therapy-predictive biomarker response [4,5], with some previous studies suggesting the relevance of host-related factors, such as the microbiota, which has been directly linked to ICI effectiveness [6,7].”
BackgroundResultGut microbiota: a potential target for improved cancer therapy
Zhao, M., Jiang, G., Zhou, H., Li, J., Xiang, W., Li, S., Wang, H., & Zhou, J. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04546-5 · Cited by 19
Alshammari, K. M., Alotaibi, F., Alsugheir, F., Aldawoud, M., Alolayan, A. A. M., Algarni, M., Sabatin, F., Mohammad, M. F., Alosaimi, A., Sanai, F. M., et al. (2023) · Cancers · doi:10.3390/cancers16010133 · Cited by 19
“However, not all patients benefit from the treatment, and our study, along with others [25–29], suggests that the use of antibiotics concurrently with ICI could contribute to reduced overall survival.”
Uncovering the role of the gut microbiota in immune checkpoint blockade therapy: A mini-review
Halsey, T. M., Ologun, G. O., Wargo, J. A., & Jenq, R. R. (2020) · Seminars in Hematology · doi:10.1053/j.seminhematol.2020.05.002 · Cited by 19
“A meta-analysis of published clinical data showed that antibiotic use reduced overall survival and progression-free survival in a majority of the profiled cases (13).”
MethodImmuno-oncology-microbiome axis of gastrointestinal malignancy
Lin, Q., Guan, S.-W., & Yu, H. (2023) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v15.i5.757 · Cited by 20
Michaelidou, K., Agelaki, S., & Mavridis, K. (2020) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2020.1724785 · Cited by 17
Classic versus innovative strategies for immuno-therapy in pancreatic cancer
Formelli, M. G., Palloni, A., Tavolari, S., Deiana, C., Andrini, E., Marco, M. D., Campana, D., Lamberti, G., & Brandi, G. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115671 · Cited by 16
Huang, L., Chen, X., Zhou, L. Q., Xu, Q., Xie, J., Zhan, P., Lv, T., & Song, Y. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-20-2076 · Cited by 15
Self-citationAnalysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy
Li, Y., Wang, S., Lin, M., Hou, C., Li, C., & Li, G. (2022) · Frontiers of Medicine · doi:10.1007/s11684-022-0927-0 · Cited by 15
The role of the microbiome in pancreatic oncogenesis
Daley, D. (2022) · International Immunology · doi:10.1093/intimm/dxac036 · Cited by 15
Zhang, W., Zhang, J., Liu, T., Xing, J., Zhang, H., Wang, D., & Tang, D. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04081-3 · Cited by 14
Wardill, H. R., Chan, R. J., Chan, A., Keefe, D. M. K., Costello, S. P., & Hart, N. H. (2022) · Supportive Care in Cancer · doi:10.1007/s00520-022-06948-0 · Cited by 13
“A recent meta-analysis reported progression-free and overall survival were negatively impacted by antibiotic use [9], suggesting that disruption of the gut microbiome’s natural, eubiotic state by antibiotics dampens anti-cancer immunity, subsequently leading to poorer clinical outcomes [10].”
BackgroundMicrobiome modulates immunotherapy response in cutaneous squamous cell carcinoma
Voigt, A. Y., Walter, A., Young, T. H., Graham, J. P., Bittencourt, B. M. B., Pulido, Á. D. M., Prieto, K., Tsai, K. Y., Sundberg, J. P., & Oh, J. (2023) · Experimental Dermatology · doi:10.1111/exd.14864 · Cited by 13
“…treatments due to their pro-apoptotic, anti-proliferative and anti- epithelial- mesenchymal-transition capabilities (reviewed in, 33 e.g. for beta-lactam antibiotics, 34,35 ) while increasingly detrimental effects on immunotherapy patient outcomes have been described (e.g. 6,7,33,36,37 ).”
Chen, H., Han, K., He, Z., & Huang, Y. (2021) · Technology in Cancer Research & Treatment · doi:10.1177/15330338211033498 · Cited by 14
Baldessari, C., Pecchi, A., Marcheselli, R., Guaitoli, G., Bonacini, R., Valoriani, F., Torricelli, P., Reverberi, L., Menozzi, R., Pugliese, G., et al. (2021) · Immunotherapy · doi:10.2217/imt-2021-0038 · Cited by 13
Amadei, S. S., & Notario, V. (2020) · Antibiotics · doi:10.3390/antibiotics9090580 · Cited by 12
Santamaria, F., Roberto, M., Buccilli, D., Civita, M. A. D., Giancontieri, P., Maltese, G., Nicolella, F., Torchia, A., Scagnoli, S., Pisegna, S., et al. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104405 · Cited by 11
Rühle, A., Zou, J., Glaser, M., Halle, L., Gkika, E., Schäfer, H. S., Knopf, A., Becker, C., Grosu, A., Popp, I., et al. (2023) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-023-07868-3 · Cited by 11
“In a recent meta-analysis, the negative prognostic effect of antibiotics in cancer patients receiving immune checkpoint inhibitors was present independently of the time of antibiotic administration in relation to immune checkpoint inhibitor treatment [19].”
BackgroundFunayama, E., Hosonuma, M., Tajima, K., Isobe, J., Baba, Y., Murayama, M., Narikawa, Y., Toyoda, H., Tsurui, T., Maruyama, Y., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117749 · Cited by 9
Dayhimi, A., Jazi, K., Bigdeli, Y., Farhoudi, F., Erfanimanesh, M., Esmaeili, M., Gorjipour, F., Ajami, M., & Pazoki–Toroudi, H. (2025) · Technology in Cancer Research & Treatment · doi:10.1177/15330338251365700 · Cited by 11
Li, C., Rich, B. E., Bullock, J. M., Barrière, O., Marier, J., & Beelen, A. P. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15549 · Cited by 9
“Administering broad-spectrum antibiotics to patients with neutropenic infections can alter the gut microbiota, an important regulator of the systemic immune system, which may additionally interfere with antitumour immune responses.(12) Trilaciclib (COSELATM; G1 Therapeutics, Inc.”
BackgroundCruellas, M., Yubero, A., Zapata, M., Galvez, E. M., Ruiz, M. G., Isla, D., Lastra, R., Martínez‐Lostao, L., Ocariz, M., Pardo, J., et al. (2021) · Infection and Immunity · doi:10.1128/iai.00665-20 · Cited by 10
Topical antibiotics limit depigmentation in a mouse model of vitiligo
Touni, A. A., Sohn, R., Cosgrove, C., Shivde, R. S., Dellacecca, E. R., Abdel-Aziz, R. T. A., Cedercreutz, K., Green, S. J., Abdel‐Wahab, H., & Poole, I. C. L. (2024) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13164 · Cited by 9
“Finally, a recent meta-analysis demonstrated a negative association between antibiotic use and the response to immune checkpoint blockade therapy in various types of cancers (Huang et al., 2019 ).”
Immune Checkpoint Inhibitors in Malignant Melanoma: Anti-PD-1, Anti-CTLA-4 and Anti-LAG-3 Therapies
Allen-Tejerina, A. M., Giannakis, P., Yau, T., Hillyar, C., & Rallis, K. S. (2026) · Current Oncology Reports · doi:10.1007/s11912-026-01750-1 · Cited by 7
“Similarly, antibiotics that alter the commensal gut flora decrease ICI efficacy across several cancer types [153, 154].”
Wu, Q., Zhang, S., Hua, X., Yu, H., & Zhong, Y. (2020) · Annals of Palliative Medicine · doi:10.21037/apm-20-1485 · Cited by 7
“Indeed, there were a few studies showing previous use of antibiotics might dampen the effect of immunotherapy (5-8).”
BackgroundHilakivi-Clarke, L. A., Verma, V., McDermott, M., Koak, P., & Andrade, F. D. O. (2022) · Frontiers in Microbiomes · doi:10.3389/frmbi.2022.1049688 · Cited by 7
“, 2021), and (ii) antibiotics that induce gut dysbiosis and eliminate critical commensal bacteria impair the effectiveness of ICBs (Huang et al., 2019; Yu et al., 2021; TsikalaVafea et al., 2021).”
BackgroundChen, J., Chen, S., Luo, H., Long, S., Yang, X., He, W., Wu, W., & Wang, S. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110919 · Cited by 7
Bonnefin, C., Schneider, S., Gerard, É., Dutriaux, C., Ferté, T., Prey, S., Guicheney, M., Ducharme, O., Pédeboscq, S., Beylot-Barry, M., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115223 · Cited by 6
Park, Y., Kang, D. H., & Chung, C. (2025) · Lung Cancer · doi:10.1016/j.lungcan.2025.108726 · Cited by 6
Deng, J., Kuang, W., Chen, W., Zhou, E., Wu, Y., Yang, Z., Chen, J., Cao, X., Yin, Z., Liu, J., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.12.014 · Cited by 6
“Emerging evidence suggests that bacteria within the tumour-associated microbiota play pivotal roles in cancer development 64 , metastasis 5 — 7 , immunosurveillance 8,65,66 and chemoresistance 9,10 .”
Haight, P. J., Kistenfeger, Q., Riedinger, C. J., Khadraoui, W. K., Backes, F. J., Bixel, K. L., Copeland, L. J., Cohn, D. E., Cosgrove, C. M., O’Malley, D. M., et al. (2023) · Gynecologic Oncology · doi:10.1016/j.ygyno.2023.09.005 · Cited by 6
Mirabile, A., Rivoltini, L., Daveri, E., Vernieri, C., Mele, R., Porcu, L., Lazzari, C., Bulotta, A., Viganò, M. G., Cascinu, S., et al. (2020) · Cancers · doi:10.3390/cancers12051153 · Cited by 5
“Moreover, the use of antibiotics during immunotherapy in cancer patients has been associated with a lower PFS and OS [29,36,146].”
BackgroundAntibiotics and Immunotherapy: Too Much of Anything is Bad!
Gopalakrishnan, V., Sellman, B. R., Cohen, T. S., & Dennis, P. A. (2020) · European Urology · doi:10.1016/j.eururo.2020.07.027 · Cited by 5
Metadata
- Authors
- Huang, X.-Z., Gao, P., Song, Y.-X., Xu, Y., Sun, J.-X., Chen, X.-W., Zhao, J.-H., & Wang, Z.-N.
- Affiliations
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University
- First Hospital of China Medical University (CN)
- Corresponding author
- Wang, Zhen-Ning
- ORCID
- Gao, Peng
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2019-09-23
- Volume
- 8
- Issue
- 12
- Pages
- e1665973-e1665973
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC6844307
- OpenAlex
- W2976586374
- Cited by
- 132
- References
- 46
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 9 · 2023: 24 · 2022: 24 · 2021: 22 · 2020: 23 · 2019: 1
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- OncoImmunology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Medical University
- 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 › Infectious Diseases › Antibiotic Use and Resistance
- Keywords
- antibiotic use, immune checkpoint inhibitors, gut microbiota, cancer immunotherapy, overall survival, progression-free survival, antitumor immunity
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