肿瘤突变负荷作为乳腺癌免疫治疗反应的预测指标。
Tumor mutational burden as a predictor of immunotherapy response in breast cancer.
作者信息
O'Meara Tess A, Tolaney Sara M
机构信息
Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
出版信息
Oncotarget. 2021 Mar 2;12(5):394-400. doi: 10.18632/oncotarget.27877.
Abstract
Tumor mutational burden (TMB) is a promising tool to help define patients with triple-negative breast cancer (TNBC) most likely to benefit from immune checkpoint blockade (ICB) therapies. Roughly reflecting the degree of neo-antigens that tumors present to immune cells, TMB associates with multiple measures of tumoral immunogenicity and has proven clinically useful in cancers with relatively high mutation burden. TNBC carries higher TMB than other breast cancer subtypes, and recent data suggest that high-TMB TNBC cases may derive particular benefit from ICB in combination with chemotherapy (GeparNuevo, IMpassion130) or even ICB alone (KEYNOTE-119, TAPUR). Given the recent approval of pembrolizumab and atezolizumab in combination with chemotherapy for PD-L1-positive, metastatic TNBC, standardizing TMB calculation methods and cut-off values is of critical importance to deploy this clinical biomarker.
摘要
肿瘤突变负荷（TMB）是一种很有前景的工具，有助于确定最有可能从免疫检查点阻断（ICB）疗法中获益的三阴性乳腺癌（TNBC）患者。TMB大致反映肿瘤呈现给免疫细胞的新抗原程度，与多种肿瘤免疫原性指标相关，并且已在具有相对高突变负荷的癌症中证明具有临床实用性。TNBC的TMB高于其他乳腺癌亚型，最近的数据表明，高TMB的TNBC病例可能从ICB联合化疗（GeparNuevo、IMpassion130）甚至单独使用ICB（KEYNOTE-119、TAPUR）中获得特别的益处。鉴于帕博利珠单抗和阿特珠单抗联合化疗最近已被批准用于PD-L1阳性转移性TNBC，标准化TMB计算方法和临界值对于应用这种临床生物标志物至关重要。
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