Tumour mutational burden (TMB), defined as the total number of somatic non-synonymous mutations present within the cancer genome, varies across and within cancer types. A first wave of retrospective and prospective research identified TMB as a predictive biomarker of response to immune-checkpoint inhibitors and culminated in the disease-agnostic approval of pembrolizumab for patients with TMB-high tumours based on data from the Keynote-158 trial. Although the applicability of outcomes from this trial to all cancer types and the optimal thresholds for TMB are yet to be ascertained, research into TMB is advancing along three principal avenues: enhancement of TMB assessments through rigorous quality control measures within the laboratory process, including the mitigation of confounding factors such as limited panel scope and low tumour purity; refinement of the traditional TMB framework through the incorporation of innovative concepts such as clonal, persistent or HLA-corrected TMB, tumour neoantigen load and mutational signatures; and integration of TMB with established and emerging biomarkers such as PD-L1 expression, microsatellite instability, immune gene expression profiles and the tumour immune contexture. Given its pivotal functions in both the pathogenesis of cancer and the ability of the immune system to recognize tumours, a profound comprehension of the foundational principles and the continued evolution of TMB are of paramount relevance for the field of oncology.

肿瘤突变负荷（TMB）定义为癌症基因组内存在的体细胞非同义突变总数，在癌症类型之间和内部存在差异。第一波回顾性和前瞻性研究将 TMB 确定为免疫检查点抑制剂反应的预测生物标志物，并最终根据 Keynote-158 试验的数据，在疾病不可知的情况下批准派姆单抗用于 TMB 高肿瘤患者。尽管该试验结果对所有癌症类型的适用性以及 TMB 的最佳阈值尚未确定，但对 TMB 的研究正在沿着三个主要途径取得进展：通过实验室过程中严格的质量控制措施来加强 TMB 评估，包括减轻混杂因素，例如有限的组合范围和低肿瘤纯度；通过结合克隆、持久或 HLA 校正 TMB、肿瘤新抗原负载和突变特征等创新概念，完善传统 TMB 框架； TMB 与已建立和新兴的生物标志物（例如 PD-L1 表达、微卫星不稳定性、免疫基因表达谱和肿瘤免疫环境）的整合。鉴于其在癌症发病机制和免疫系统识别肿瘤的能力中的关键功能，对 TMB 基本原理的深刻理解和持续进化对于肿瘤学领域至关重要。