The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer

Immune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in non‐small‐cell lung cancer (NSCLC), but our understanding of biomarkers that predict the response to ICB remain obscure. Here we integrated somatic mutational profile and clinicopathologic information from 113 NSCLC...

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Bibliographic Details
Published in:Cancer science 2019-08, Vol.110 (8), p.2348-2356
Main Authors: Chen, Hao, Chong, Wei, Teng, Changcai, Yao, Yueliang, Wang, Xin, Li, Xue
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
APOBEC signature
Apolipoprotein B
Apoptosis
B7-H1 Antigen - genetics
B7-H1 Antigen - immunology
Biomarkers, Tumor - genetics
Biomarkers, Tumor - immunology
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - immunology
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Female
Gene expression
Generalized linear models
Genomes
Genomics
Humans
Immune checkpoint
immune checkpoint blockade
Immunity - genetics
Immunity - immunology
Immunologic Memory - genetics
Immunological memory
Immunoregulation
Immunotherapy
Infiltration
Killer Cells, Natural - immunology
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lymphocytes
Lymphocytes T
Male
Medical prognosis
Memory cells
Metastases
Middle Aged
Mismatch repair
mRNA
Mutation
Mutation - genetics
Mutation - immunology
Natural killer cells
neoantigen burden
Neoantigens
Non-small cell lung carcinoma
non‐small‐cell lung cancer
Original
Patients
PD-L1 protein
Progression-Free Survival
Proteins
PTEN protein
Regression analysis
RNA editing
Smoking
Statistical analysis
Survival analysis
T-Lymphocytes, Regulatory - immunology
Tumor Burden - genetics
Tumor Burden - immunology
tumor mutation burden
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Summary:Immune checkpoint blockade (ICB) therapy has achieved remarkable clinical benefit in non‐small‐cell lung cancer (NSCLC), but our understanding of biomarkers that predict the response to ICB remain obscure. Here we integrated somatic mutational profile and clinicopathologic information from 113 NSCLC patients treated by ICB (CTLA‐4/PD‐1). High tumor mutation burden (TMB) and neoantigen burden were identified significantly associated with improved efficacy in NSCLC immunotherapy. Furthermore, we identified apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like (APOBEC) mutational signature was markedly associated with responding of ICB therapy (log‐rank test, P = .001; odds ratio (OR), 0.18 [95% CI, 0.06‐0.50], P 
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.14113