Peixoto Renata D'Alpino, Mathias-Machado Maria Cecilia, Jácome Alexandre, Gil Mariana, Fogacci João, Sodré Bárbara, Passarini Thaís, Chaves Aline, Diniz Paulo Henrique, Lino Flora, Palladino Alexandre, Souto Mirela, de Castro Ana Carolina, Garicochea Bernardo
Department of Gastrointestinal Medical Oncology, Oncoclinicas, São Paulo, Brazil.
Department of Gastrointestinal Medical Oncology, Oncoclinicas, Belo Horizonte, Brazil.
J Gastrointest Oncol. 2023 Jun 30;14(3):1560-1575. doi: 10.21037/jgo-22-1133. Epub 2023 May 11.
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.
In the present comprehensive review, we revised the main studies regarding PD-L1 evaluation in GC.
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.
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.
免疫检查点抑制开启了癌症治疗的新纪元,随机临床试验表明,相当一部分转移性胃癌(GC)患者群体可能从免疫治疗中获得临床益处,这凸显了识别预测性生物标志物的重要性。程序性细胞死亡配体1(PD-L1)表达已显示出其在GC中的表达水平与免疫检查点抑制所带来的获益程度之间存在显著关联。然而,在将免疫检查点抑制纳入GC标准治疗的治疗决策中,该生物标志物存在一些必须考虑的缺陷,如空间和时间异质性、观察者间变异性、免疫组织化学(IHC)检测以及化疗或放疗的影响。
在本综述中,我们回顾了关于GC中PD-L1评估的主要研究。
在此,我们描述了GC肿瘤微环境的分子特征、PD-L1表达解读中的障碍,并呈现了评估免疫检查点抑制疗效和安全性以及与生物标志物表达相关性的临床试验数据,涵盖一线和后续治疗。
在免疫检查点抑制的新兴预测性生物标志物中,PD-L1已显示出肿瘤微环境中的表达水平与GC中免疫检查点抑制所带来的获益程度之间存在有意义的关联。