The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
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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Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722 · cited 1×
“15).(38-40) To assess the bias risk of an individual study on the results and to investigate the stability and consistency of our results, sensitivity analyses were conducted to investigate whether a single study dominated the results by a leave-one-out approach (individually omitting each study).”
ResultOperating characteristics of a rank correlation test for publication bias
Begg, C. B., & Mazumdar, M. (1994) · Biometrics · doi:10.2307/2533446 · Cited by 16,955 · cited 1×
“15).(38-40) To assess the bias risk of an individual study on the results and to investigate the stability and consistency of our results, sensitivity analyses were conducted to investigate whether a single study dominated the results by a leave-one-out approach (individually omitting each study).”
ResultDuval, S., & Tweedie, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00455.x · Cited by 14,099 · cited 1×
“15).(38-40) To assess the bias risk of an individual study on the results and to investigate the stability and consistency of our results, sensitivity analyses were conducted to investigate whether a single study dominated the results by a leave-one-out approach (individually omitting each study).”
ResultPD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · cited 1×
“ICI immunotherapy has revolutionized cancer therapy for several solid tumors, and the anti-tumor response to ICIs is enhanced by inhibiting the PD-1 or CTLA-4 pathways and subsequently reactivating the host’s immune function.(30-32) Although the Table 1.”
BackgroundGut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671 · cited 6×
“Furthermore, preclinical studies have reported that the gut microbiota is involved in the response to ICI immunotherapy.(9,10) Moreover, it has been is well-documented that antibiotics (ATBs) can alter the diversity and composition of the commensal gut microbiota.”
BackgroundResultInfluentialPrimary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025 · cited 1×
“ICI immunotherapy has revolutionized cancer therapy for several solid tumors, and the anti-tumor response to ICIs is enhanced by inhibiting the PD-1 or CTLA-4 pathways and subsequently reactivating the host’s immune function.(30-32) Although the Table 1.”
BackgroundGut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812 · cited 1×
“, Ruminococcaceae family, Faecalibacterium, and Akkermansia muciniphila).(10,33) In addition, several studies have reported that the anti-tumor effects of ICIs were improved in germ-free or ATB-treated mice receiving a fecal microbiota transplantation from responders rather than non-responders, and a favorable gut mic…”
BackgroundInteractions Between the Microbiota and the Immune System
Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012) · Science · doi:10.1126/science.1223490 · Cited by 4,173 · cited 2×
“The negative association between ATB use and the clinical efficacy of ICI immunotherapy verified the results of previous studies reporting that the diversity and composition of the gut microbiota play a critical role in the immune response.(7,10) Indeed, Matson et al.”
BackgroundResultThe commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients
Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M.-L., Luke, J. J., & Gajewski, T. F. (2018) · Science · doi:10.1126/science.aao3290 · Cited by 3,107 · cited 4×
“In addition, several studies have reported that the anti-tumor effects of ICIs were improved in germ-free or ATB-treated mice receiving a fecal microbiota transplantation from responders rather than non-responders, and a favorable gut microbiota could enhance antigen presentation and T cell function associated with th…”
BackgroundInfluential
Cited by
Sorted by citations
The microbiome and human cancer
Sepich-Poore, G. D., Zitvogel, L., Straussman, R., Hasty, J., Wargo, J. A., & Knight, R. (2021) · Science · doi:10.1126/science.abc4552 · Cited by 1,332
(2023) · doi:10.1038/s41392-022-01304-4 · Cited by 460
“Increasing clinical data suggest that systemic use of antibiotics can lead to less effective immune checkpoint inhibitors.(235,236) In addition, several studies in patients with lung, colon, and pancreatic cancer have shown that removal of the tumor microbiota can enhance the inflammatory process of the tumor, inhibit…”
Backgroundγδ T cells: origin and fate, subsets, diseases and immunotherapy
Hu, Y., Hu, Q., Li, Y., Lu, L., Xiang, Z., Yin, Z., Kabelitz, D., & Wu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01653-8 · Cited by 418
Tomita, Y., Ikeda, T., Sakata, S., Saruwatari, K., Sato, R., Iyama, S., Jodai, T., Akaike, K., Ishizuka, S., Saeki, S., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0051 · Cited by 256
“Probiotic CBT improved ICB efficacy in antibiotic-treated patients Antibiotic therapy before the start of ICB therapy reduces response to ICB (1, 3, 4, 7).”
BackgroundResultInfluentialIntestinal microbiota influences clinical outcome and side effects of early breast cancer treatment
Terrisse, S., Derosa, L., Iebba, V., Ghiringhelli, F., Vaz-Luis, I., Kroemer, G., Fidelle, M., Christodoulidis, S., Segata, N., Thomas, A. M., et al. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-021-00784-1 · Cited by 172
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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