Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01620
Keywords
cyclin D1(CCND1); immune checkpoint inhibitors; prognosis; tumor microenvironment; biomarker
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Funding
- Fujian Provincial Health and Family Planning Research Talent Training Program [2018-ZQN-13, 2018-CX-11]
- Joint Funds for the Innovation of Science and Technology, Fujian Province [2017Y9077, 2018Y9107]
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Cyclin D1 (CCND1)amplification relevant to malignant biological behavior exists in solid tumors. The prevalence and utility ofCCND1amplification as a biomarker for the clinical response to treatment with immune checkpoint inhibitors (ICIs) are unknown. Our study is a preliminary investigation mainly focused on the predictive function ofCCND1amplification in the tumor microenvironment (TME) in the aspect of genome and transcriptome. We examined the prevalence ofCCND1amplification and its potential as a biomarker for the efficacy of ICI therapy for solid tumors using a local database (n= 6,536), The Cancer Genome Atlas (TCGA) database (n= 10,606), and the Memorial Sloan Kettering Cancer Center (MSKCC) database (n= 10,109). Comprehensive profiling was performed to determine the prevalence ofCCND1amplification and the correlation with the prognosis and the response to ICIs. ACCND1amplification occurs in many cancer types and correlates with shorter overall survival and inferior outcomes with ICI therapy. Transcriptomic analysis showed various degrees of immune cell exclusion, including cytotoxic cells, T cells, CD8(+)T cells, dendritic cells (DCs), and B cells in the TME in a TCGACCND1amplification population. The gene set enrichment analysis suggested thatCCND1amplification correlates with multiple aggressive, immunosuppressive hallmarks including epithelial-mesenchymal transition, transforming growth factor (TGF)-beta signaling, KRAS signaling, phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling, p53 pathway, and hypoxia signaling in solid tumors. These findings indicate thatCCND1amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs.
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