Huang Xuan-Zhang, Gao Peng, Song Yong-Xi, Xu Yan, Sun Jing-Xu, Chen Xiao-Wan, Zhao Jun-Hua, Wang Zhen-Ning
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, Shenyang, China.
Oncoimmunology. 2019 Sep 23;8(12):e1665973. doi: 10.1080/2162402X.2019.1665973. eCollection 2019.
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; < .001), without heterogeneity (I = 0.0%; = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49-2.26; < .001; I = 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.
肠道微生物群在抗肿瘤免疫反应中起着关键作用。越来越多的数据表明，抗生素会改变肠道微生物群的组成，并影响免疫检查点抑制剂（ICI）的疗效。然而，这是第一项评估抗生素使用与癌症患者ICI疗效之间关联的荟萃分析，以便更好地了解这种关联的强度。我们使用PubMed、Embase和会议数据库对评估抗生素使用与ICI疗效之间关系的相关研究进行了文献检索。主要结局包括通过风险比（HR）和相应的95%置信区间（CI）衡量的总生存期（OS）和无进展生存期（PFS）。还进行了亚组分析和敏感性分析。分析共纳入了19项符合条件的研究，包括2740例接受ICI治疗的癌症患者。我们的结果表明，抗生素使用与癌症患者的OS呈负相关（HR = 2.37；95% CI = 2.05 - 2.75；P <.001），无异质性（I² = 0.0%；P = 0.851）。此外，抗生素使用显著降低了接受ICI治疗患者的PFS（HR = 1.84；95% CI = 1.49 - 2.26；P <.001；I² = 56.2%）。在按抗生素使用时间和癌症类型分层的亚组分析中也获得了类似结果。敏感性分析证实了我们结果的稳定性。因此，我们荟萃分析的结果表明，抗生素使用与接受ICI免疫治疗的癌症患者的OS和PFS呈负相关。
