APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer

Abstract

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.

Publication
Oncogene. 2018 Apr 26. doi: 10.1038/s41388-018-0245-9
Date

Here we report through systematic cancer genomics and transcriptomic association studies that APOBEC3B overexpression is associated with immune gene expression and known immunotherapy response biomarkers, APOBEC mutational signature is specifically enriched in patients with durable clinical benefit (DCB) after immunotherapy and APOBEC mutation count can be better than total mutation count in predicting immunotherapy response. Our study implicates APOBEC3B and APOBEC mutational signature as novel predictive biomarkers for checkpoint blockade immunotherapy response in NSCLC.