Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy

Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biom...

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Bibliographic Details
Published in:Cancers 2021-04, Vol.13 (7), p.1639
Main Authors: Sun, Shangqin, Xu, Liwen, Zhang, Xinxin, Pang, Lin, Long, Zhilin, Deng, Chunyu, Zhu, Jiali, Zhou, Shuting, Wan, Linyun, Pang, Bo, Xiao, Yun
Format: Article
Language:English
Subjects:
Biomarkers
Cancer immunotherapy
CTLA-4 protein
Datasets
Gene expression
Immune checkpoint
Immune response
Immunotherapy
Liver cancer
Lymphocytes
Melanoma
Non-small cell lung carcinoma
Patients
PD-1 protein
PD-L1 protein
Principal components analysis
Response rates
Sample size
Small cell lung carcinoma
Survival analysis
Transcriptomes
Urothelial cancer
γ-Interferon
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Summary:Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biomarkers remains insufficient. We collected 22 transcriptome-based biomarkers for ICB response and constructed multiple benchmark datasets to evaluate the associations with clinical response, predictive performance, and clinical efficacy of them in pre-treatment patients with distinct ICB agents in diverse cancers. Overall, "Immune-checkpoint molecule" biomarkers PD-L1, PD-L2, CTLA-4 and IMPRES and the "Effector molecule" biomarker CYT showed significant associations with ICB response and clinical outcomes. These immune-checkpoint biomarkers and another immune effector IFN-gamma presented predictive ability in melanoma, urothelial cancer (UC) and clear cell renal-cell cancer (ccRCC). In non-small cell lung cancer (NSCLC), only PD-L2 and CTLA-4 showed preferable correlation with clinical response. Under different ICB therapies, the top-performing biomarkers were usually mutually exclusive in patients with anti-PD-1 and anti-CTLA-4 therapy, and most of biomarkers presented outstanding predictive power in patients with combined anti-PD-1 and anti-CTLA-4 therapy. Our results show these biomarkers had different performance in predicting ICB response across distinct ICB agents in diverse cancers.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13071639