PMID- 32903763
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20240329
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - CCND1 Amplification Contributes to Immunosuppression and Is Associated With a 
      Poor Prognosis to Immune Checkpoint Inhibitors in Solid Tumors.
PG  - 1620
LID - 10.3389/fimmu.2020.01620 [doi]
LID - 1620
AB  - Cyclin D1 (CCND1) amplification relevant to malignant biological behavior exists 
      in solid tumors. The prevalence and utility of CCND1 amplification 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 of CCND1 amplification in the tumor microenvironment (TME) in 
      the aspect of genome and transcriptome. We examined the prevalence of CCND1 
      amplification 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 of CCND1 amplification and the correlation with the prognosis and 
      the response to ICIs. A CCND1 amplification 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 TCGA CCND1 amplification population. The gene set 
      enrichment analysis suggested that CCND1 amplification 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 that CCND1 amplification 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.
CI  - Copyright (c) 2020 Chen, Huang, Gao, Li, Lin, Chen, Chang, Chen, Guan, Pan, Xia, 
      Guo, Pan, Xu, Yi and Chen.
FAU - Chen, Yu
AU  - Chen Y
AD  - Department of Medical Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
FAU - Huang, Yingying
AU  - Huang Y
AD  - Fujian Medical University Cancer Hospital, Fuzhou, China.
FAU - Gao, Xuan
AU  - Gao X
AD  - Geneplus-Beijing, Beijing, China.
FAU - Li, Yi
AU  - Li Y
AD  - Fujian Medical University Cancer Hospital, Fuzhou, China.
FAU - Lin, Jing
AU  - Lin J
AD  - Department of Medical Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
FAU - Chen, Lizhu
AU  - Chen L
AD  - Department of Medical Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
FAU - Chang, Lianpeng
AU  - Chang L
AD  - Geneplus-Beijing, Beijing, China.
FAU - Chen, Gang
AU  - Chen G
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
AD  - Department of Pathology, Fujian Medical University Cancer Hospital & Fujian 
      Cancer Hospital, Fuzhou, China.
FAU - Guan, Yanfang
AU  - Guan Y
AD  - Geneplus-Beijing, Beijing, China.
FAU - Pan, Leong Kin
AU  - Pan LK
AD  - CCIC Group, Kuok Kim (Macao) Medical Center III, Macao, China.
AD  - Hui Xian Medical Center, Macao, China.
FAU - Xia, Xuefeng
AU  - Xia X
AD  - Geneplus-Beijing, Beijing, China.
FAU - Guo, Zengqing
AU  - Guo Z
AD  - Department of Medical Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
FAU - Pan, Jianji
AU  - Pan J
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
AD  - Department of Radiation Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
FAU - Xu, Yaping
AU  - Xu Y
AD  - Geneplus-Beijing, Beijing, China.
FAU - Yi, Xin
AU  - Yi X
AD  - Geneplus-Beijing, Beijing, China.
FAU - Chen, Chuanben
AU  - Chen C
AD  - Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
AD  - Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
AD  - Department of Radiation Oncology, Fujian Medical University Cancer Hospital & 
      Fujian Cancer Hospital, Fuzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200810
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCND1 protein, human)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 136601-57-5 (Cyclin D1)
SB  - IM
MH  - *Biomarkers, Tumor
MH  - Computational Biology/methods
MH  - Cyclin D1/*genetics
MH  - *Gene Amplification
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immune Checkpoint Inhibitors/pharmacology/therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology
MH  - Molecular Targeted Therapy
MH  - Mutation
MH  - Neoplasms/diagnosis/drug therapy/*etiology/*mortality
MH  - Prognosis
MH  - Treatment Outcome
MH  - Tumor Escape/*genetics/*immunology
MH  - Tumor Microenvironment/genetics/immunology
PMC - PMC7438829
OTO - NOTNLM
OT  - biomarker
OT  - cyclin D1 (CCND1)
OT  - immune checkpoint inhibitors
OT  - prognosis
OT  - tumor microenvironment
EDAT- 2020/09/10 06:00
MHDA- 2021/04/20 06:00
PMCR- 2020/01/01
CRDT- 2020/09/09 17:57
PHST- 2020/01/15 00:00 [received]
PHST- 2020/06/17 00:00 [accepted]
PHST- 2020/09/09 17:57 [entrez]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01620 [doi]
PST - epublish
SO  - Front Immunol. 2020 Aug 10;11:1620. doi: 10.3389/fimmu.2020.01620. eCollection 
      2020.