Tumor mutational burden (TMB) reflects cancer mutation quantity. Mutations are processed to neo-antigens and presented by major histocompatibility complex (MHC) proteins to T cells. To evade immune eradication, cancers exploit checkpoints that dampen T cell reactivity. Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enabling T cell reactivation; however, response biomarkers are required, as most patients do not benefit. Higher TMB results in more neo-antigens, increasing chances for T cell recognition, and clinically correlates with better ICI outcomes. Nevertheless, TMB is an imperfect response biomarker. A composite predictor that also includes critical variables, such as MHC and T cell receptor repertoire, is needed.

肿瘤突变负荷（TMB）反映了癌症突变的数量。突变被加工成新抗原，并由主要组织相容性复合体 (MHC) 蛋白呈递给 T 细胞。为了逃避免疫根除，癌症利用抑制 T 细胞反应性的检查点。免疫检查点抑制剂 (ICIs) 通过使 T 细胞重新激活而改变了癌症治疗方法；然而，需要反应生物标志物，因为大多数患者不会受益。较高的 TMB 会产生更多的新抗原，增加 T 细胞识别的机会，并且在临床上与更好的 ICI 结果相关。然而，TMB 是一种不完美的反应生物标志物。需要一个还包括关键变量（例如 MHC 和 T 细胞受体库）的复合预测因子。