Department of Biochemistry, School of Medicine, University of Crete, Voutes, 71013, Heraklion, Crete, Greece.
Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
Cell Oncol (Dordr). 2019 Apr;42(2):237-242. doi: 10.1007/s13402-018-00419-7. Epub 2019 Jan 25.
The levels of expression and membrane localization of programmed cell death ligand 1 (PD-L1), an immune checkpoint type I transmembrane glycoprotein, are related to the clinical response of anti-PD-L1/PD-1 therapy. Although the biologically relevant localization of PD-L1 is on the plasma membrane of cancer cells, it has also been reported to be in the cytoplasm and sometimes in the nucleus. Furthermore, it has been claimed that chemotherapeutics can modify PD-L1 expression and/or its nuclear localization.
Data from our group suggest that the nuclear localization of PD-L1, and other plasma membrane proteins as well, could be an artifact resulting from inadequate experimental conditions during immunocytochemical studies. Mild detergent and rigorous fixation conditions should be used in order to preserve the membrane localization and to prevent an erroneous translocation of PD-L1 and other non-interconnected membrane proteins, such as CD24, into other cellular compartments including the nucleus, of untreated and chemotherapeutically treated breast cancer cells.
We propose that well-specified and rigorously followed protocols should be applied to immunocytochemical diagnostic techniques, especially to those related to individualized diagnosis and treatment.
程序性细胞死亡配体 1（PD-L1）是一种免疫检查点 I 型跨膜糖蛋白，其表达水平和膜定位与抗 PD-L1/PD-1 治疗的临床反应有关。虽然 PD-L1 的生物学相关定位是在癌细胞的质膜上，但也有报道称其位于细胞质中，有时甚至位于细胞核中。此外，有人声称化学疗法可以改变 PD-L1 的表达和/或其核定位。
我们小组的数据表明，PD-L1 的核定位以及其他质膜蛋白的核定位可能是免疫细胞化学研究中实验条件不充分的结果。为了保留膜定位并防止 PD-L1 和其他非连接膜蛋白（如 CD24）错误转位到其他细胞区室，包括未经处理和化疗处理的乳腺癌细胞的细胞核，应使用温和的去污剂和严格的固定条件。
我们建议应将经过精心制定和严格遵循的方案应用于免疫细胞化学诊断技术，特别是那些与个体化诊断和治疗相关的技术。
