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

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...

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Bibliographic Details
Published inOncogene Vol. 37; no. 29; pp. 3924 - 3936
Main Authors Wang, Shixiang, Jia, Mingming, He, Zaoke, Liu, Xue-Song
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.07.2018
Nature Publishing Group
Subjects
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45/70
631/67/1059/2325
631/67/1612/1350
631/67/69
692/53/2423
Apolipoproteins
Apoptosis
Biochemistry
Biological markers
Care and treatment
Cell Biology
Cytidine deaminase
Development and progression
Gene expression
Gene mutation
Genes
Genetic aspects
Health aspects
Human Genetics
Immune checkpoint
Immunotherapy
Internal Medicine
Lung cancer
Lymphocytes T
Medicine
Medicine & Public Health
Methods
Mutation
Non-small cell lung cancer
Non-small cell lung carcinoma
Oncology
Patient outcomes
PD-L1 protein
Prognosis
Small cell lung cancer
Smoking
T cells
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Summary: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.
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ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-018-0245-9