Division of Medical Oncology, Department of Medicine, School of Medicine, Showa University, Tokyo, Japan.
Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan.
Front Immunol. 2023 Sep 18;14:1260492. doi: 10.3389/fimmu.2023.1260492. eCollection 2023.
Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.
In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.
PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.
Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.
肿瘤组织中程序性死亡配体 1（PD-L1）的表达被测量为许多癌症类型中免疫检查点抑制剂（ICI）治疗效果的预测因子。PD-L1 表达通过使用 3,3´-二氨基联苯胺（DAB）chronogenesis（IHC-DAB）的免疫组织化学染色进行评估；然而，仍然存在定量和可重复性问题。我们专注于使用荧光纳米粒子磷整合点（PID）的高度敏感的定量免疫组织化学方法，并评估了 PID 方法和传统 DAB 方法之间的 PD-L1 表达。
总共从四所大学医院招募了 155 名接受 ICI 治疗的转移性或复发性癌症患者。在治疗前收集的肿瘤组织标本通过 PID 和传统 DAB 方法进行免疫组织化学染色，以评估 PD-L1 蛋白表达。
使用 PID 和 DAB 方法评估的 PD-L1 表达呈正相关。我们使用 PID 方法对 PD-L1 表达进行了定量，并计算了 PD-L1 PID 评分。应答者组的 PID 评分明显高于无应答者组。生存分析表明，使用 IHC-DAB 方法评估的 PD-L1 表达与无进展生存期（PFS）或总生存期（OS）无关。然而，PD-L1 PID 评分高的患者的 PFS 和 OS 显著延长。
作为 PID 评分的 PD-L1 表达的定量评估在预测接受 ICI 治疗的癌症患者的治疗效果和预后方面更为有效。使用 PID 方法对 PD-L1 表达的定量评估是一种新的蛋白质检测策略。PID 方法能够识别出一组用传统 DAB 方法无法识别的预后良好的患者，这具有重要意义。
