The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.
The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.
复制标题
DOI：
10.1126/science.aao3290
复制
发表时间：
2018-01-05
期刊：
影响因子：
--
通讯作者：
Gajewski TF
中科院分区：
文献类型：
--
作者：
Matson V;Fessler J;Bao R;Chongsuwat T;Zha Y;Alegre ML;Luke JJ;Gajewski TF
基于抗PD-1的免疫疗法对癌症治疗产生了重大影响，但只使一小部分患者受益。在可能导致患者间异质性的变量中，患者微生物组的不同组成已被证明影响临床前小鼠模型的抗肿瘤免疫和免疫治疗效果。我们在免疫治疗前分析了转移性黑色素瘤患者的基线粪便样本，通过对选定细菌的16S核糖体RNA基因测序、超基因组鸟枪测序和定量聚合酶链式反应的整合。观察到共生微生物组成和临床反应之间存在显著的相关性。应答者中含量较高的细菌种类包括长双歧杆菌、柯林塞氏菌和粪肠球菌。用有反应的患者的粪便材料重建无菌小鼠可以改善肿瘤控制，增强T细胞反应，并提高抗PD-L1治疗的效果。我们的结果表明，共生微生物群可能对人类癌症患者的抗肿瘤免疫产生机械性影响。
Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients’ microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.
登录
查看更多内容
影响因子：
28.2
作者：
Peng W;Chen JQ;Liu C;Malu S;Creasy C;Tetzlaff MT;Xu C;McKenzie JA;Zhang C;Liang X;Williams LJ;Deng W;Chen G;Mbofung R;Lazar AJ;Torres-Cabala CA;Cooper ZA;Chen PL;Tieu TN;Spranger S;Yu X;Bernatchez C;Forget MA;Haymaker C;Amaria R;McQuade JL;Glitza IC;Cascone T;Li HS;Kwong LN;Heffernan TP;Hu J;Bassett RL Jr;Bosenberg MW;Woodman SE;Overwijk WW;Lizée G;Roszik J;Gajewski TF;Wargo JA;Gershenwald JE;Radvanyi L;Davies MA;Hwu P
通讯作者：
Hwu P
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
DOI：
10.1126/science.aac4255
发表时间：
2015-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sivan A;Corrales L;Hubert N;Williams JB;Aquino-Michaels K;Earley ZM;Benyamin FW;Lei YM;Jabri B;Alegre ML;Chang EB;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
64.8
作者：
Spranger, Stefani;Bao, Riyue;Gajewski, Thomas F.
通讯作者：
Gajewski, Thomas F.