Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.
Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.
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进展期黑色素瘤患者肠道微生物组与免疫检查点抑制反应的相关性。
DOI：
10.1038/s41591-022-01695-5
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发表时间：
2022-03
期刊：
影响因子：
82.9
通讯作者：
Segata N
中科院分区：
文献类型：
--
作者：
Lee KA;Thomas AM;Bolte LA;Björk JR;de Ruijter LK;Armanini F;Asnicar F;Blanco-Miguez A;Board R;Calbet-Llopart N;Derosa L;Dhomen N;Brooks K;Harland M;Harries M;Leeming ER;Lorigan P;Manghi P;Marais R;Newton-Bishop J;Nezi L;Pinto F;Potrony M;Puig S;Serra-Bellver P;Shaw HM;Tamburini S;Valpione S;Vijay A;Waldron L;Zitvogel L;Zolfo M;de Vries EGE;Nathan P;Fehrmann RSN;Bataille V;Hospers GAP;Spector TD;Weersma RK;Segata N
肠道微生物组的组成与免疫检查点抑制剂 (ICI) 治疗的临床反应有关，但对于与 ICI 临床益处相关的特定微生物组特征的共识有限。我们对 ICI 开始前收集的粪便样本进行了鸟枪法宏基因组测序，这些样本来自招募未接受过 ICI 的晚期皮肤黑色素瘤患者的五个观察队列 (n = 165)。将数据集与先前发表的研究中的 147 个宏基因组样本整合，我们发现肠道微生物组与 ICI 的反应具有相关但依赖于队列的关联。机器学习分析证实了微生物组与 ICI 的总体缓解率 (ORR) 和无进展生存期 (PFS) 之间的联系，但也揭示了基于微生物组的特征在各队列中的再现性有限。因此，包括假链状双歧杆菌、罗斯伯利亚属在内的一组物种。和 Akkermansia muciniphila 与反应者相关，但没有一个物种可以被视为跨研究完全一致的生物标志物。总体而言，人类肠道微生物组在 ICI 反应中的作用似乎比之前想象的更为复杂，超出了反应者和非反应者中简单存在或不存在的不同微生物种类。未来的研究应采用更大的样本量，并考虑治疗过程中临床因素与肠道微生物组的复杂相互作用。对接受免疫检查点阻断治疗的多个黑色素瘤患者粪便样本进行宏基因组测序分析，揭示了微生物组与治疗反应的相关性，并揭示了不同人群之间广泛的变异性。
The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course. An analysis of metagenomic sequencing of stool samples from multiple cohorts of patients with melanoma treated with immune checkpoint blockade uncovers microbiome correlates of response to therapy and also reveals widespread variability across populations.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7.7
作者：
Beghini F;McIver LJ;Blanco-Míguez A;Dubois L;Asnicar F;Maharjan S;Mailyan A;Manghi P;Scholz M;Thomas AM;Valles-Colomer M;Weingart G;Zhang Y;Zolfo M;Huttenhower C;Franzosa EA;Segata N
通讯作者：
Segata N
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
56.9
作者：
Heithoff, DM;Sinsheimer, RL;Mahan, MJ
通讯作者：
Mahan, MJ