Elbehi Attia M
Department of Oncology, Medical Sciences Division, University of Oxford, Oxford, UK.
Camb Prism Precis Med. 2024 Dec 20;3:e3. doi: 10.1017/pcm.2024.6. eCollection 2025.
The discovery and development of immune checkpoint inhibitors (ICIs) has revolutionised the management of human cancers. However, only a subset of patients responds to ICI therapy, even though immune evasion is a hallmark of cancer. Initially, treatment was administered to patients on the basis of expression levels of one of the targets of ICI therapy, programmed cell death ligand 1. In clinical trials, the high response rate of melanoma and non-small cell lung cancer patients to ICI therapy supported the basic premise of cancer immunotherapy, that tumour-specific mutated proteins trigger an immune response. Tumour mutational burden subsequently emerged as a potential biomarker for response to ICI therapy. This review summarises the evidence supporting the scientific rationale for TMB as a biomarker for ICI therapy and focuses on some of the major challenges associated with incorporation of TMB into routine clinical practice.
免疫检查点抑制剂（ICI）的发现与开发彻底改变了人类癌症的治疗方式。然而，尽管免疫逃逸是癌症的一个标志，但只有一部分患者对ICI治疗有反应。最初，根据ICI治疗靶点之一程序性细胞死亡配体1的表达水平对患者进行治疗。在临床试验中，黑色素瘤和非小细胞肺癌患者对ICI治疗的高反应率支持了癌症免疫治疗的基本前提，即肿瘤特异性突变蛋白会引发免疫反应。肿瘤突变负荷随后成为ICI治疗反应的潜在生物标志物。本综述总结了支持将肿瘤突变负荷作为ICI治疗生物标志物的科学依据的证据，并重点关注将肿瘤突变负荷纳入常规临床实践所面临的一些主要挑战。
