Xiong Wenjun, Gao Yang, Wei Wenyi, Zhang Jinfang
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Trends Cancer. 2021 Sep;7(9):837-846. doi: 10.1016/j.trecan.2021.03.003. Epub 2021 Apr 23.
Although targeting programmed death 1/programmed death ligand 1 (PD-1/PD-L1) has achieved durable responses and disease remission in patients with certain cancers, relatively low response rates and emerging resistance limit its clinical application. Hence, a more thorough understanding of regulatory mechanisms of the PD-1/PD-L1 axis is vital for developing combined therapeutic strategies to overcome hurdles of PD-1/PD-L1 blockade. Increasing evidence has demonstrated that PD-L1 can be secreted into the extracellular space or translocated into the nucleus, which also plays a critical role in regulating cancer immune evasion, tumorigenesis, and immunotherapy. In this review, we summarize these emerging roles of extracellular and nuclear PD-L1 and discuss future research directions and potential opportunities in translational medicine.
尽管靶向程序性死亡1/程序性死亡配体1（PD-1/PD-L1）已在某些癌症患者中实现了持久反应和疾病缓解，但相对较低的反应率和新出现的耐药性限制了其临床应用。因此，更深入地了解PD-1/PD-L1轴的调控机制对于制定联合治疗策略以克服PD-1/PD-L1阻断的障碍至关重要。越来越多的证据表明，PD-L1可以分泌到细胞外空间或转运到细胞核中，这在调节癌症免疫逃逸、肿瘤发生和免疫治疗中也起着关键作用。在这篇综述中，我们总结了细胞外和细胞核PD-L1的这些新作用，并讨论了转化医学的未来研究方向和潜在机会。
