Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma.
Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma.
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DOI：
10.1186/s13073-021-00974-z
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发表时间：
2021-10-13
期刊：
影响因子：
12.3
通讯作者：
Ahn J
中科院分区：
文献类型：
--
作者：
Usyk M;Pandey A;Hayes RB;Moran U;Pavlick A;Osman I;Weber JS;Ahn J
免疫检查点阻断(ICB)在晚期黑色素瘤中显示出持久的益处；然而，并不是所有的患者对这种治疗都有反应，许多人会出现潜在的威胁生命的免疫相关不良事件(IrAE)。为了提高护理质量，确定将发展为irAEs的个人是至关重要的。在这里，我们前瞻性地证明，肠道微生物组可以预测接受ICB的黑色素瘤患者的irAEs。27例晚期黑色素瘤患者在纽约大学朗格尼健康中心接受IPI(抗CTLA-4)和Nivo(抗PD1)ICB抑制剂治疗后，采集了治疗前、治疗中和治疗后的粪便样本。我们完成了16S rRNA基因扩增序列、DNA深鸟枪元基因组和RNA序列元转录测序。采用除法放大去噪算法(DADA2)处理16S数据。使用MetaPhlAn2指定鸟枪式测序数据的分类，并使用Humann 2.0指定基因路径。使用ANCOM进行成分感知差异表达分析。使用Cox比例风险模型评估肠道微生物群(GMB)在irAES中的预期作用，并对年龄、性别、BMI、免疫ICB治疗类型和测序批次进行调整。通过对16SRRNA数据的分析，确定了两个具有不同群落组成的天然绿色微生物群(R2=0.16p<；0.001)。在Cox比例风险模型中，这两组患者在开始治疗后一年内发生irAEs的风险差异接近7倍(HR=6.89[95%CI：1.33-35.58])。利用鸟枪元基因组学，我们进一步鉴定了37株在风险组之间差异表达的细菌，其中多雷类杆菌在高风险组中具有特定的优势，而普通类杆菌在低风险组中具有特殊的优势。高危人群似乎也有几个功能通路的表达升高，包括那些与腺苷代谢相关的通路(均为FDR<；0.05)。对基线和治疗开始后6周和12周的样本(n=10名参与者)进行的子分析显示，微生物群在整个治疗过程中保持稳定(R2=0.88，p<；0.001)。我们确定了两个不同的粪便细菌群落，它们与ICB治疗的晚期黑色素瘤患者的irAEs有不同的关联。网上版载有补充材料，可在10.1186/s13073-021-00974-z查阅。
Immune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB. Pre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch. Two natural GMB clusters with distinct community compositions were identified from the analysis of 16S rRNA data (R2 = 0.16, p < 0.001). In Cox-proportional hazard modeling, these two clusters showed a near 7-fold differential risk for developing irAEs within 1 year of initiating treatment (HR = 6.89 [95% CI: 1.33–35.58]). Using shotgun metagenomics, we further identified 37 bacterial strains differentially expressed between the risk groups, with specific dominance of Bacteroides dorei within the high-risk GMB cluster and Bacteroides vulgatus in the low-risk cluster. The high-risk cluster also appeared to have elevated expression of several functional pathways, including those associated with adenosine metabolism (all FDR < 0.05). A sub-analysis of samples (n = 10 participants) at baseline and 6 and 12 weeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R2 = 0.88, p < 0.001). We identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients. The online version contains supplementary material available at 10.1186/s13073-021-00974-z.
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人参多糖改变了肠道菌群和kynurenine/色氨酸的比例，增强了抗编程细胞死亡1/程序性细胞死亡配体1（抗PD-1/PD-1/PD-L1）免疫疗法的抗肿瘤效应。
影响因子：
24.5
作者：
Huang J;Liu D;Wang Y;Liu L;Li J;Yuan J;Jiang Z;Jiang Z;Hsiao WW;Liu H;Khan I;Xie Y;Wu J;Xie Y;Zhang Y;Fu Y;Liao J;Wang W;Lai H;Shi A;Cai J;Luo L;Li R;Yao X;Fan X;Wu Q;Liu Z;Yan P;Lu J;Yang M;Wang L;Cao Y;Wei H;Leung EL
通讯作者：
Leung EL
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K