Abstract:
UNASSIGNED: Immune checkpoint inhibition has shed light on a new era in cancer therapy, and randomized clinical trials have demonstrated that a meaningful portion of the overall population of metastatic gastric cancer (GC) patients may derive clinical benefit from immunotherapy, which raises the relevance in identifying predictive biomarkers. Programmed cell death-ligand 1 (PD-L1) expression has demonstrated a significant association between level of expression and the magnitude of benefit derived from immune checkpoint inhibition in GC. Nevertheless, this biomarker shows several pitfalls that must be considered in the therapeutic decision to incorporate immune checkpoint inhibition as the standard of care of GC, such as spatial and temporal heterogeneity, interobserver variability, immunohistochemistry (IHC) assay, and influence by chemotherapy or radiation therapy.
UNASSIGNED: In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC.
UNASSIGNED: Here we describe the molecular characteristics of the tumor microenvironment in GC, the obstacles in the interpretation of PD-L1 expression and present the data of the clinical trials that have evaluated the efficacy and safety of immune checkpoint inhibition and the association with the biomarker expression, both in first-line and later lines of therapy.
UNASSIGNED: From the emerging predictive biomarkers for immune checkpoint inhibition, PD-L1 has demonstrated a meaningful association between level of expression in tumor microenvironment and the magnitude of benefit derived from immune checkpoint inhibition in GC.
摘要:
■免疫检查点抑制揭示了癌症治疗的新时代,和随机临床试验表明,转移性胃癌(GC)患者的整体人群中有一部分可能从免疫治疗中获得临床益处,这提高了识别预测性生物标志物的相关性。程序性细胞死亡配体1(PD-L1)表达已证明表达水平与GC中免疫检查点抑制产生的益处之间存在显着关联。然而,这种生物标志物显示了在将免疫检查点抑制作为GC护理标准的治疗决策中必须考虑的几个陷阱,如时空异质性,观察者间的可变性,免疫组织化学(IHC)测定,以及化疗或放疗的影响。
■在本次全面审查中,我们修订了关于GC中PD-L1评估的主要研究。
■在这里,我们描述了GC中肿瘤微环境的分子特征,解释PD-L1表达的障碍,并提供评估免疫检查点抑制的有效性和安全性以及与生物标志物表达的关联的临床试验数据,在一线和后期治疗中。
■从免疫检查点抑制的新兴预测生物标志物,PD-L1已证明肿瘤微环境中的表达水平与来自GC中免疫检查点抑制的益处之间有意义的关联。