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| Status |
Public on Aug 04, 2024 |
| Title |
The PKCα/ZFP64/CSF1 Axis restricts Tumor Response to Anti-PD1 by driving Macrophage M2 Polarization in Hepatocellular Carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Despite remarkable achievements, majority of hepatocellular carcinoma (HCC) patients fail to respond to anti-PD1 therapy. Here, we showed that ZFP64 was frequently upregulated in HCC tissues of anti-PD1 resistance patients. Elevated ZFP64 levels triggered tumor progression and induced an immunosuppressive microenvironment. Mechanistically, ZFP64 transcriptionally activated colony-stimulating factor 1 (CSF1) by directly binding to its promoter, and secreted CSF1 driving the shift of macrophages into an alternatively activated phenotype. Importantly, the PKCα was revealed to phosphorylate ZFP64 at S226, resulting in its nuclear translocation to transcribe the CSF1 gene. Particularly, we proposed firstly that the PKCα/ZFP64/CSF1 axis was a critical pathway in fostering immune evasion and anti-PD1 tolerance and inhibiting this axis with lenvatinib or Gö6976 surmounted the anti-PD1 resistance in HCC. Our study indicates that the ZFP64 is an emerging indicator in predicting anti-PD1 efficacy, and reveals the PKCα/ZFP64/CSF1 axis is a suitable target for anti-PD1 combination therapy in HCC.
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| Overall design |
ChIP-Seq analysis in PLC/PRF/5 cells with ZFP64 overexpression.
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| Contributor(s) |
Wei C, Fan J |
| Citation missing |
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| Submission date |
Aug 04, 2021 |
| Last update date |
Aug 04, 2024 |
| Contact name |
Chuan Yuan Wei |
| E-mail(s) |
18111210068@fudan.edu.cn
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| Phone |
13262679886
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| Organization name |
Zhongshan, Fudan
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| Department |
Liver cancer institute
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| Lab |
Jia Fan's Lab
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| Street address |
fenglin road 180
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA752043 |
| SRA |
SRP331073 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE181436_PLC-Flag_peaks.narrow.annotation.xlsx |
2.8 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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