Abstract:
Cancer immunotherapy holds great promise and has shown durable responses in many patients; however, these responses are not uniform in all patients or all tumour streams. There is an ongoing clinical need for objective diagnostic biomarkers to identify patients that will respond to immunotherapies. Tumour mutational burden (TMB) is a diagnostic biomarker that can stratify cancer patients for response to immune checkpoint inhibitor therapies. It is commonly defined as the average number of somatic mutations per megabase in a tumour exome. Here we describe the TMB biomarker, how it is determined, its underlying molecular basis, the relationship to neoantigens and the issues around its clinical use. This overview is directed toward practising pathologists wishing to be informed of this predictive biomarker.
摘要:
癌症免疫疗法具有巨大的前景,并在许多患者中显示出持久的反应;然而,这些反应在所有患者或所有肿瘤流中都不一致。临床上仍需要客观的诊断生物标志物来鉴定将对免疫疗法有反应的患者。肿瘤突变负荷(TMB)是一种诊断性生物标志物,可以对癌症患者对免疫检查点抑制剂疗法的反应进行分层。它通常被定义为肿瘤外显子组中每兆碱基的体细胞突变的平均数。在这里,我们描述了TMB生物标志物,它是如何确定的,其潜在的分子基础,与新抗原的关系及其临床使用的问题。该概述针对希望被告知该预测性生物标志物的执业病理学家。