Vanpouille-Box Claire, Lhuillier Claire, Bezu Lucillia, Aranda Fernando, Yamazaki Takahiro, Kepp Oliver, Fucikova Jitka, Spisek Radek, Demaria Sandra, Formenti Silvia C, Zitvogel Laurence, Kroemer Guido, Galluzzi Lorenzo
Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Université Paris Descartes/Paris V, Paris, France.
Oncoimmunology. 2017 Aug 31;6(11):e1373237. doi: 10.1080/2162402X.2017.1373237. eCollection 2017.
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity. Tailoring the delivery of specific ICBs or combinations thereof to selected patient populations in the context of precision medicine programs constitutes indeed a major objective of the future of ICB-based immunotherapy. Here, we discuss recent preclinical and clinical advances on the development of ICBs for oncological indications.
免疫检查点阻断剂(ICB)确实正在彻底改变越来越多样化的一系列肿瘤适应症的临床管理。尽管围绕细胞毒性T淋巴细胞相关蛋白4(CTLA4)和程序性细胞死亡1(PDCD1,最广为人知的是PD-1)信号通路的抑制仍备受关注,但其他几种共抑制性T细胞受体正作为新型ICB开发的潜在靶点进行评估。此外,人们正在投入大量精力来识别生物标志物,这些标志物能够可靠地预测每个患者在无严重毒性的情况下从ICB获得临床益处的可能性。在精准医学计划的背景下,为选定的患者群体量身定制特定ICB或其组合的给药确实构成了基于ICB的免疫治疗未来的一个主要目标。在此,我们讨论ICB用于肿瘤适应症开发的最新临床前和临床进展。