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肺癌免疫治疗的预测生物标志物:国际肺癌研究协会病理学委员会的观点。

Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee.

机构信息

Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts.

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.

出版信息

J Thorac Oncol. 2022 Dec;17(12):1335-1354. doi: 10.1016/j.jtho.2022.09.109. Epub 2022 Sep 29.

Abstract

Immunotherapy including immune checkpoint inhibitors (ICIs) has become the backbone of treatment for most lung cancers with advanced or metastatic disease. In addition, they have increasingly been used for early stage tumors in neoadjuvant and adjuvant settings. Unfortunately, however, only a subset of patients experiences meaningful response to ICIs. Although programmed death-ligand 1 (PD-L1) protein expression by immunohistochemistry (IHC) has played a role as the principal predictive biomarker for immunotherapy, its performance may not be optimal, and it suffers multiple practical issues with different companion diagnostic assays approved. Similarly, tumor mutational burden (TMB) has multiple technical issues as a predictive biomarker for ICIs. Now, ongoing research on tumor- and host immune-specific factors has identified immunotherapy biomarkers that may provide better response and prognosis prediction, in particular in a multimodal approach. This review by the International Association for the Study of Lung Cancer Pathology Committee provides an overview of various immunotherapy biomarkers, including updated data on PD-L1 IHC and TMB, and assessments of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, and microbiome and pathologic response to neoadjuvant immunotherapies. The aim of this review is to underline the efficacy of new individual or combined predictive biomarkers beyond PD-L1 IHC and TMB.

摘要

免疫疗法包括免疫检查点抑制剂(ICI)已成为治疗大多数晚期或转移性肺癌的主要方法。此外,它们在新辅助和辅助治疗中也越来越多地用于早期肿瘤。然而,不幸的是,只有一部分患者对 ICI 有明显的反应。尽管免疫组织化学(IHC)检测程序性死亡配体 1(PD-L1)蛋白表达已成为免疫治疗的主要预测生物标志物,但它的性能可能并不理想,并且在不同批准的伴随诊断检测中存在多种实际问题。同样,肿瘤突变负担(TMB)作为 ICI 的预测生物标志物也存在多种技术问题。目前,对肿瘤和宿主免疫特异性因素的研究已经确定了免疫治疗生物标志物,这些标志物可能提供更好的反应和预后预测,特别是在多模式方法中。国际肺癌研究协会病理学委员会的这篇综述概述了各种免疫治疗生物标志物,包括 PD-L1 IHC 和 TMB 的最新数据,以及对新抗原、遗传和表观遗传特征、免疫组织化学和转录组学的免疫微环境以及微生物组和对新辅助免疫治疗的病理反应的评估。本综述的目的是强调除 PD-L1 IHC 和 TMB 之外,新的个体或联合预测生物标志物的疗效。

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