School of Life Science and Technology, ShanghaiTech University, Shanghai, 201203, China.
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Oncogene. 2018 Jul;37(29):3924-3936. doi: 10.1038/s41388-018-0245-9. Epub 2018 Apr 26.
Non-small cell lung cancer (NSCLC) is known to carry heavy mutation load. Besides smoking, cytidine deaminase APOBEC3B plays a key role in the mutation process of NSCLC. APOBEC3B is also reported to be upregulated and predicts bad prognosis in NSCLC. However, targeting APOBEC3B high NSCLC is still a big challenge. Here we show that APOBEC3B upregulation is significantly associated with immune gene expression, and APOBEC3B expression positively correlates with known immunotherapy response biomarkers, including: PD-L1 expression and T-cell infiltration in NSCLC. Importantly, APOBEC mutational signature is specifically enriched in NSCLC patients with durable clinical benefit after immunotherapy and APOBEC mutation count can be better than total mutation in predicting immunotherapy response. In together, this work provides evidence that APOBEC3B upregulation and APOBEC mutation count can be used as novel predictive markers in guiding NSCLC checkpoint blockade immunotherapy.
非小细胞肺癌（NSCLC）已知具有较高的突变负荷。除了吸烟，胞嘧啶脱氨酶 APOBEC3B 在 NSCLC 的突变过程中起着关键作用。有报道称 APOBEC3B 上调并预测 NSCLC 的不良预后。然而，针对 APOBEC3B 高表达的 NSCLC 仍然是一个巨大的挑战。我们发现 APOBEC3B 的上调与免疫基因表达显著相关，并且 APOBEC3B 的表达与已知的免疫治疗反应生物标志物呈正相关，包括 NSCLC 中的 PD-L1 表达和 T 细胞浸润。重要的是，APOBEC 突变特征在免疫治疗后具有持久临床获益的 NSCLC 患者中特异性富集，并且 APOBEC 突变计数在预测免疫治疗反应方面可能优于总突变计数。总之，这项工作为 APOBEC3B 上调和 APOBEC 突变计数可作为指导 NSCLC 检查点阻断免疫治疗的新型预测标志物提供了证据。
