Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers.
Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers.
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DOI：
10.1038/s41467-017-01018-0
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发表时间：
2017-10-19
影响因子：
16.6
通讯作者：
Lee JS
中科院分区：
文献类型：
--
作者：
Ock CY;Hwang JE;Keam B;Kim SB;Shim JJ;Jang HJ;Park S;Sohn BH;Cha M;Ajani JA;Kopetz S;Lee KW;Kim TM;Heo DS;Lee JS
免疫疗法已成为一种有前途的抗癌治疗方法，然而，人们对决定免疫疗法反应的遗传特征知之甚少。我们开发了免疫治疗反应的转录预测因子，并评估其对 30 种不同癌症类型的约 10,000 个人体组织的基因组数据的预测，以估计对免疫治疗的潜在反应。综合分析揭示了两种不同的肿瘤类型：突变类型与免疫治疗的潜在反应呈正相关，而染色体不稳定类型与之呈负相关。我们发现体细胞突变和拷贝数改变与免疫治疗的潜在反应显着相关，特别是抗 CTLA-4 抗体治疗。我们的研究结果表明，肿瘤可能通过两种不同的途径进化，这将导致免疫治疗反应的显着差异以及逃避免疫监视的不同策略。我们的分析提供了资源，以促进免疫治疗预测生物标志物的发现，这些生物标志物可以在临床试验中进行测试。迫切需要确定用于选择免疫治疗反应者的预测标记。在这里，作者描述了免疫治疗反应的转录预测因子，并在来自 30 种不同癌症类型的约 10,000 个人体组织的基因组数据中对其进行了评估。
Immunotherapy has emerged as a promising anti-cancer treatment, however, little is known about the genetic characteristics that dictate response to immunotherapy. We develop a transcriptional predictor of immunotherapy response and assess its prediction in genomic data from ~10,000 human tissues across 30 different cancer types to estimate the potential response to immunotherapy. The integrative analysis reveals two distinct tumor types: the mutator type is positively associated with potential response to immunotherapy, whereas the chromosome-instable type is negatively associated with it. We identify somatic mutations and copy number alterations significantly associated with potential response to immunotherapy, in particular treatment with anti-CTLA-4 antibody. Our findings suggest that tumors may evolve through two different paths that would lead to marked differences in immunotherapy response as well as different strategies for evading immune surveillance. Our analysis provides resources to facilitate the discovery of predictive biomarkers for immunotherapy that could be tested in clinical trials. There is an urgent need to identify predictive markers for selecting responders to immunotherapy. Here, the authors describe a transcriptional predictor of immunotherapy response and assess it in genomic data from ~ 10,000 human tissues across 30 different cancer types.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS