Siniard Rance C, Harada Shuko
Department of Pathology, University of Alabama at Birmingham, 1802 6th Avenue South, NP3540, Birmingham, AL, 35249, USA.
Virchows Arch. 2017 Aug;471(2):209-219. doi: 10.1007/s00428-017-2140-0. Epub 2017 May 20.
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy. A T cell-dependent mechanism of cancer progression was discovered in 2012, providing a potential link to cancer immunotherapy. Since then, an antibody against cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), ipilimumab, and three programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq), were approved by the Food and Drug Administration (FDA) in the USA. In this review article, based on evidence that has been emerging in the literature over the last decade, we will discuss the basis for including genomic data in immunotherapy regimens, the current progress in identifying biomarkers targetable by immune checkpoint blockade, and the application of these therapies in modern oncology programs. Going forward, the clinical application of NGS in personalized oncology programs could include dose monitoring and adjustment or the development of individualized vaccines or other personalized therapies based on the mutational landscape. The continued identification of new neoantigens and the efficient mobilization of tumor-reactive lymphocytes in patients with cancer will promote the advancement of immunotherapy using personalized NGS-guided technologies.
虽然基因组数据的应用有可能彻底改变患者护理,但在将宿主 - 肿瘤相互作用转化为对患者有利的临床结果方面仍有许多工作要做。高通量技术,如下一代测序(NGS),迅速提升了我们对肿瘤学的理解,并且我们了解到大多数肿瘤并非简单地拥有负责肿瘤发生的持续突变基因,这促使了个性化癌症治疗的需求。2012年发现了一种依赖T细胞的癌症进展机制,为癌症免疫治疗提供了潜在联系。从那时起,一种抗细胞毒性T淋巴细胞相关分子4(CTLA - 4)的抗体伊匹单抗,以及三种程序性死亡1(PD - 1)/程序性死亡配体1(PD - L1)抑制剂帕博利珠单抗(可瑞达)、纳武利尤单抗(欧狄沃)和阿特珠单抗(泰圣奇)先后获得美国食品药品监督管理局(FDA)批准。在这篇综述文章中,基于过去十年文献中不断涌现的证据,我们将讨论在免疫治疗方案中纳入基因组数据的依据、识别可被免疫检查点阻断靶向的生物标志物的当前进展,以及这些疗法在现代肿瘤学项目中的应用。展望未来,NGS在个性化肿瘤学项目中的临床应用可能包括剂量监测与调整,或基于突变图谱开发个性化疫苗或其他个性化疗法。持续识别新的新抗原以及有效调动癌症患者体内的肿瘤反应性淋巴细胞,将推动使用个性化NGS引导技术的免疫治疗的发展。