Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.
Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.
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DOI：
10.1038/s41588-018-0200-2
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发表时间：
2018-09
期刊：
影响因子：
30.8
通讯作者：
Van Allen EM
中科院分区：
文献类型：
--
作者：
Miao D;Margolis CA;Vokes NI;Liu D;Taylor-Weiner A;Wankowicz SM;Adeegbe D;Keliher D;Schilling B;Tracy A;Manos M;Chau NG;Hanna GJ;Polak P;Rodig SJ;Signoretti S;Sholl LM;Engelman JA;Getz G;Jänne PA;Haddad RI;Choueiri TK;Barbie DA;Haq R;Awad MM;Schadendorf D;Hodi FS;Bellmunt J;Wong KK;Hammerman P;Van Allen EM
在多种实体瘤中，肿瘤突变负荷与对免疫检查点阻断的反应相关，尽管在微卫星稳定肿瘤中，这种关联很弱，临床实用性有限。在这里，我们统一分析了249个肿瘤的全外显子组测序（WES），并将来自具有临床注释结果的患者的正常组织与免疫检查点治疗相匹配，包括放射学反应，在多种癌症类型中检查有助于选择性反应的其他肿瘤基因组特征。我们的分析确定了突变负荷以外的反应的基因组相关性，包括个体驱动基因中的体细胞事件、某些全局突变特征和特定的HLA限制性新抗原。然而，这些特征通常是相互关联的，突出了识别产生免疫应答肿瘤环境的遗传驱动事件的复杂性。这项研究为以综合和多方面的方式分析大型临床队列奠定了基础，以提高我们发现免疫检查点阻断反应的临床有意义的预测特征的能力。
Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, though in microsatellite stable tumors this association is weak and of limited clinical utility. Here, we uniformly analyzed whole exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often inter-related, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance our ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1158/1078-0432.ccr-16-3133
发表时间：
2017-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kato S;Goodman A;Walavalkar V;Barkauskas DA;Sharabi A;Kurzrock R
通讯作者：
Kurzrock R
DOI：
10.1126/science.1253462
发表时间：
2014-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Bruin EC;McGranahan N;Mitter R;Salm M;Wedge DC;Yates L;Jamal-Hanjani M;Shafi S;Murugaesu N;Rowan AJ;Grönroos E;Muhammad MA;Horswell S;Gerlinger M;Varela I;Jones D;Marshall J;Voet T;Van Loo P;Rassl DM;Rintoul RC;Janes SM;Lee SM;Forster M;Ahmad T;Lawrence D;Falzon M;Capitanio A;Harkins TT;Lee CC;Tom W;Teefe E;Chen SC;Begum S;Rabinowitz A;Phillimore B;Spencer-Dene B;Stamp G;Szallasi Z;Matthews N;Stewart A;Campbell P;Swanton C
通讯作者：
Swanton C
影响因子：
11.2
作者：
Colli LM;Machiela MJ;Myers TA;Jessop L;Yu K;Chanock SJ
通讯作者：
Chanock SJ