Dubin Krista, Callahan Margaret K, Ren Boyu, Khanin Raya, Viale Agnes, Ling Lilan, No Daniel, Gobourne Asia, Littmann Eric, Huttenhower Curtis, Pamer Eric G, Wolchok Jedd D
Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Nat Commun. 2016 Feb 2;7:10391. doi: 10.1038/ncomms10391.
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.
肠道微生物群的组成会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具有挑战性，因为临床上可检测到的炎症及其治疗会改变微生物群的组成。用伊匹单抗进行免疫检查点阻断，伊匹单抗是一种阻断细胞毒性T淋巴细胞相关抗原4（CTLA-4）信号传导的单克隆抗体，与新发的免疫介导性结肠炎有关。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组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比例增加与对检查点阻断诱导的结肠炎发展的抗性相关。此外，参与多胺转运和B族维生素生物合成的遗传途径缺乏与结肠炎风险增加有关。识别这些生物标志物可能有助于采取干预措施，以降低癌症免疫治疗后炎症并发症的风险。
