Department of Medical Oncology, Center GF Leclerc, Dijon, France; Research Platform in Biological Oncology, Dijon, France; GIMI Genetic and Immunology Medical Institute, Dijon, France; University of Burgundy-Franche Comté, Dijon, France; UMR INSERM 1231, Dijon, France.
Research Platform in Biological Oncology, Dijon, France; GIMI Genetic and Immunology Medical Institute, Dijon, France; UMR INSERM 1231, Dijon, France.
Eur J Cancer. 2020 May;131:40-50. doi: 10.1016/j.ejca.2020.02.038. Epub 2020 Apr 9.
Treatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by CD8 T cells, resulting in improved immune responses. In this review, we will discuss rationale and implementation of TMB usage in patients, development of different methods to assess it, current limitations and technical issues to use this biomarker as a diagnostic test and propose future perspectives beyond TMB.
治疗针对程序性细胞死亡蛋白 1（PD-1）或其配体（PD-L1）的免疫检查点抑制剂可以在多种癌症类型中产生持久的反应，但仅在一部分患者中。因此，预测 PD-1/PD-L1 抑制剂反应的生物标志物对于患者选择至关重要。PD-L1 的表达已被证明在患者选择中具有一定的作用。肿瘤突变负担（TMB）是一种新的 PD-1/PD-L1 抑制剂反应生物标志物。该生物标志物的评估基于以下假设：体细胞外显子区域的大量突变会导致新抗原的产生增加，然后这些新抗原可以被 CD8 T 细胞识别，从而增强免疫反应。在这篇综述中，我们将讨论 TMB 在患者中的应用原理和实施情况，不同评估方法的发展，目前的局限性和使用该生物标志物作为诊断测试的技术问题，并提出除 TMB 以外的未来展望。
