Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211019442. doi: 10.1177/15330338211019442.
In recent years, immunotherapies have emerged as effective therapeutic strategies for treating human cancers. However, accumulating evidence has revealed an inconsistency between the response to immune checkpoint inhibitors and programmed death ligand 1 (PD-L1) expression status detected by immunohistochemistry staining. Recent research has revealed that the removal of N-Linked glycosylation significantly enhanced PD-L1 detection, resulting in both more accurate PD-L1 quantification and clinical outcome prediction. In the present study, we evaluated natural and deglycosylated PD-L1 expression in colon cancer using the PD-L1 28-8 antibody. The results of the present study validated the hypothesis that PD-L1 had a higher expression in colon cancer tissues compared with normal tissues. Additionally, colon tumors with defective mismatch repair tended to express higher PD-L1 than those without. Most importantly, the results of the present study indicated that the removal of N-linked glycosylation remarkably enhanced PD-L1 detection. Moreover, the PD-L1 signal intensity of samples with a low natural PD-L1 signal was enhanced more remarkably than that of samples with high signal intensity. Overall, our research provides an improved strategy for patient stratification for anti-PD-1/PD-L1 therapy, which deepens the clinical significance of this established strategy for treatment of colon cancer.
近年来,免疫疗法已成为治疗人类癌症的有效治疗策略。然而,越来越多的证据表明,免疫检查点抑制剂的反应与免疫组织化学染色检测到的程序性死亡配体 1(PD-L1)表达状态之间存在不一致性。最近的研究表明,去除 N-连接糖基化可显著增强 PD-L1 的检测,从而实现更准确的 PD-L1 定量和临床结果预测。在本研究中,我们使用 PD-L1 28-8 抗体评估了结肠癌中天然和去糖基化 PD-L1 的表达。本研究的结果验证了 PD-L1 在结肠癌组织中的表达高于正常组织的假设。此外,具有错配修复缺陷的结肠肿瘤比没有错配修复缺陷的结肠肿瘤表达更高的 PD-L1。最重要的是,本研究结果表明,去除 N-连接糖基化可显著增强 PD-L1 的检测。此外,与高信号强度的样本相比,天然 PD-L1 信号强度低的样本的 PD-L1 信号强度增强更为显著。总体而言,我们的研究为抗 PD-1/PD-L1 治疗的患者分层提供了一种改进的策略,深化了这一既定策略治疗结肠癌的临床意义。