Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.
Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.
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DOI：
10.1038/ncomms10391
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发表时间：
2016-02-02
影响因子：
16.6
通讯作者：
Wolchok JD
中科院分区：
文献类型：
--
作者：
Dubin K;Callahan MK;Ren B;Khanin R;Viale A;Ling L;No D;Gobourne A;Littmann E;Huttenhower C;Pamer EG;Wolchok JD
肠道微生物群的组成影响炎症性疾病的发展。然而，将炎症性疾病与微生物群的特定微生物成员联系起来是具有挑战性的，因为临床上可检测到的炎症及其治疗可以改变微生物群的组成。伊匹单抗（一种阻断细胞毒性T淋巴细胞相关抗原-4（CTLA-4）信号传导的单克隆抗体）的免疫检查点阻断与新发免疫介导的结肠炎相关。在这里，我们对接受伊匹单抗治疗的转移性黑色素瘤患者进行了一项前瞻性研究，并将炎症前粪便微生物群和微生物群组成与随后的结肠炎发展相关联。我们证明，属于拟杆菌门的细菌的代表性增加与对检查点阻断诱导的结肠炎的发展的抗性相关。此外，参与多胺转运和B族维生素生物合成的遗传途径的缺乏与结肠炎风险的增加有关。这些生物标志物的鉴定可能使干预措施能够降低癌症免疫治疗后炎症并发症的风险。 接受免疫检查点阻断治疗的一部分癌症患者发生结肠炎。在这里，作者表明，黑色素瘤患者粪便样品中拟杆菌和维生素B生物合成模块的丰度较低可以预测他们在抗CTLA-4治疗后对结肠炎的易感性。
The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. A subset of cancer patients treated with immune checkpoint blockade develops colitis. Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.