General Information
- Project ID
- OEP003755
- Project Name
- An inflammatory checkpoint generated by IL1RN splicing offers therapeutic opportunity for KRAS mutant intrahepatic cholangiocarcinoma
- Description
- KRAS mutations are causally linked to pro-tumor inflammation and identified as driving factors in tumorigenesis. Here, using multi-omics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS mutant iCCA. In KRAS mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant anti-tumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti-PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in KRAS mutant iCCA patients were significantly associated with superior response to anti-PD-1 immunotherapy.
- Publications
-
An inflammatory checkpoint generated by IL1RN splicing offers therapeutic opportunity for KRAS mutant intrahepatic cholangiocarcinoma.
Zhang, Mao et al. “An inflammatory checkpoint generated by IL1RN splicing offers therapeutic opportunity for KRAS mutant intrahepatic cholangiocarcinoma.” Cancer discovery, CD-23-0282. 24 Jul. 2023
(PMID: 37486241) (DOI: 10.1158/2159-8290.CD-23-0282) - Related Links
- https://www.biosino.org/node/project/detail/OEP002560 https://www.biosino.org/node/project/detail/OEP001105
Project information
- Experiments
- 3
- Samples
- 60
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES287008 YA-1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287009 YA-2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287010 YA-3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287011 YA-4 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287012 YA-5 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287013 YA-6 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287014 YAK-1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287015 YAK-2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287016 YAK-3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287017 YAK-4 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287018 YAK-5 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287019 YAK-6 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287020 YAK_Vector-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287021 YAK_Vector-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287022 YAK_Vector-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287023 YAK_IL1RN-201-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287024 YAK_IL1RN-201-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287025 YAK_IL1RN-201-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287026 YAK_IL1RN-203-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287027 YAK_IL1RN-203-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287028 YAK_IL1RN-203-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287029 YAK_Vector_Anakinra-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287030 YAK_Vector_Anakinra-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287031 YAK_Vector_Anakinra-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287032 YAK_IgG-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287033 YAK_IgG-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287034 YAK_IgG-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287035 YAK_PD1-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287036 YAK_PD1-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287037 YAK_PD1-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287038 YAK_Anakinra_IgG-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287039 YAK_Anakinra_IgG-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287040 YAK_Anakinra_IgG-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287041 YAK_Anakinra_PD1-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287042 YAK_Anakinra_PD1-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287043 YAK_Anakinra_PD1-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287044 YA_IgG-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287045 YA_IgG-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287046 YA_IgG-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287047 YA_PD1-S1 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287048 YA_PD1-S2 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES287049 YA_PD1-S3 Animalia Mus musculus Intrahepatic Cholangiocarcinoma tissue 2022-11-20 OES294992 LICCF_shNC-1 Cell line Homo sapiens cell line 2023-02-16 OES294993 LICCF_shNC-2 Cell line Homo sapiens cell line 2023-02-16 OES294994 LICCF_shNC-3 Cell line Homo sapiens cell line 2023-02-16 OES294995 LICCF_sh_IL1RN-201-1 Cell line Homo sapiens cell line 2023-02-16 OES294996 LICCF_sh_IL1RN-201-2 Cell line Homo sapiens cell line 2023-02-16 OES294997 LICCF_sh_IL1RN-201-3 Cell line Homo sapiens cell line 2023-02-16 OES294998 HuCCT1_Vector-1 Cell line Homo sapiens cell line 2023-02-16 OES294999 HuCCT1_Vector-2 Cell line Homo sapiens cell line 2023-02-16 OES295000 HuCCT1_Vector-3 Cell line Homo sapiens cell line 2023-02-16 OES295001 HuCCT1_IL1RN-201-1 Cell line Homo sapiens cell line 2023-02-16 OES295002 HuCCT1_IL1RN-201-2 Cell line Homo sapiens cell line 2023-02-16 OES295003 HuCCT1_IL1RN-201-3 Cell line Homo sapiens cell line 2023-02-16 OES295004 HuCCT1_Vector-4 Cell line Homo sapiens cell line 2023-02-16 OES295005 HuCCT1_Vector-5 Cell line Homo sapiens cell line 2023-02-16 OES295006 HuCCT1_Vector-6 Cell line Homo sapiens cell line 2023-02-16 OES295007 HuCCT1_IL1RN-203-1 Cell line Homo sapiens cell line 2023-02-16 OES295008 HuCCT1_IL1RN-203-2 Cell line Homo sapiens cell line 2023-02-16 OES295009 HuCCT1_IL1RN-203-3 Cell line Homo sapiens cell line 2023-02-16 - Runs
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90
Run ID Run Name Experiment Sample Data Num Create Date OER378509 LICCF_shNC-1_RNASeq-1 OEX021095 OES294992 1 2023-02-16 OER378510 LICCF_shNC-1_RNASeq-2 OEX021095 OES294992 1 2023-02-16 OER378511 LICCF_shNC-2_RNASeq-1 OEX021095 OES294993 1 2023-02-16 OER378512 LICCF_shNC-2_RNASeq-2 OEX021095 OES294993 1 2023-02-16 OER378513 LICCF_shNC-3_RNASeq-1 OEX021095 OES294994 1 2023-02-16 OER378514 LICCF_shNC-3_RNASeq-2 OEX021095 OES294994 1 2023-02-16 OER378515 LICCF_sh_IL1RN-201-1_RNASeq-1 OEX021095 OES294995 1 2023-02-16 OER378516 LICCF_sh_IL1RN-201-1_RNASeq-2 OEX021095 OES294995 1 2023-02-16 OER378517 LICCF_sh_IL1RN-201-2_RNASeq-1 OEX021095 OES294996 1 2023-02-16 OER378518 LICCF_sh_IL1RN-201-2_RNASeq-2 OEX021095 OES294996 1 2023-02-16 OER378519 LICCF_sh_IL1RN-201-3_RNASeq-1 OEX021095 OES294997 1 2023-02-16 OER378520 LICCF_sh_IL1RN-201-3_RNASeq-2 OEX021095 OES294997 1 2023-02-16 OER378521 HuCCT1_Vector-1_RNASeq-1 OEX021095 OES294998 1 2023-02-16 OER378522 HuCCT1_Vector-1_RNASeq-2 OEX021095 OES294998 1 2023-02-16 OER378523 HuCCT1_Vector-2_RNASeq-1 OEX021095 OES294999 1 2023-02-16 OER378524 HuCCT1_Vector-2_RNASeq-2 OEX021095 OES294999 1 2023-02-16 OER378525 HuCCT1_Vector-3_RNASeq-1 OEX021095 OES295000 1 2023-02-16 OER378526 HuCCT1_Vector-3_RNASeq-2 OEX021095 OES295000 1 2023-02-16 OER378527 HuCCT1_IL1RN-201-1_RNASeq-1 OEX021095 OES295001 1 2023-02-16 OER378528 HuCCT1_IL1RN-201-1_RNASeq-2 OEX021095 OES295001 1 2023-02-16 OER378529 HuCCT1_IL1RN-201-2_RNASeq-1 OEX021095 OES295002 1 2023-02-16 OER378530 HuCCT1_IL1RN-201-2_RNASeq-2 OEX021095 OES295002 1 2023-02-16 OER378531 HuCCT1_IL1RN-201-3_RNASeq-1 OEX021095 OES295003 1 2023-02-16 OER378532 HuCCT1_IL1RN-201-3_RNASeq-2 OEX021095 OES295003 1 2023-02-16 OER378533 HuCCT1_Vector-4_RNASeq-1 OEX021095 OES295004 1 2023-02-16 OER378534 HuCCT1_Vector-4_RNASeq-2 OEX021095 OES295004 1 2023-02-16 OER378535 HuCCT1_Vector-5_RNASeq-1 OEX021095 OES295005 1 2023-02-16 OER378536 HuCCT1_Vector-5_RNASeq-2 OEX021095 OES295005 1 2023-02-16 OER378537 HuCCT1_Vector-6_RNASeq-1 OEX021095 OES295006 1 2023-02-16 OER378538 HuCCT1_Vector-6_RNASeq-2 OEX021095 OES295006 1 2023-02-16 OER378539 HuCCT1_IL1RN-203-1_RNASeq-1 OEX021095 OES295007 1 2023-02-16 OER378540 HuCCT1_IL1RN-203-1_RNASeq-2 OEX021095 OES295007 1 2023-02-16 OER378541 HuCCT1_IL1RN-203-2_RNASeq-1 OEX021095 OES295008 1 2023-02-16 OER378542 HuCCT1_IL1RN-203-2_RNASeq-2 OEX021095 OES295008 1 2023-02-16 OER378543 HuCCT1_IL1RN-203-3_RNASeq-1 OEX021095 OES295009 1 2023-02-16 OER378544 HuCCT1_IL1RN-203-3_RNASeq-2 OEX021095 OES295009 1 2023-02-16 OER378545 YAK_Vector-S1_scRNA OEX021096 OES287020 2 2023-02-16 OER378546 YAK_Vector-S2_scRNA OEX021096 OES287021 6 2023-02-16 OER378547 YAK_Vector-S3_scRNA OEX021096 OES287022 4 2023-02-16 OER378548 YAK_IgG-S1_scRNA OEX021096 OES287032 2 2023-02-16 OER378549 YAK_IgG-S2_scRNA OEX021096 OES287034 2 2023-02-16 OER378550 YAK_IgG-S3_scRNA OEX021096 OES287033 2 2023-02-16 OER378551 YAK_PD1-S1_scRNA OEX021096 OES287035 2 2023-02-16 OER378552 YAK_PD1-S2_scRNA OEX021096 OES287036 2 2023-02-16 OER378553 YAK_PD1-S3_scRNA OEX021096 OES287037 2 2023-02-16 OER378554 YAK_Anakinra_IgG-S1_scRNA OEX021096 OES287029 2 2023-02-16 OER378555 YAK_Anakinra_IgG-S2_scRNA OEX021096 OES287030 2 2023-02-16 OER378556 YAK_Anakinra_IgG-S3_scRNA OEX021096 OES287031 2 2023-02-16 OER378557 YAK_Anakinra_PD1-S1_scRNA OEX021096 OES287041 2 2023-02-16 OER378558 YAK_Anakinra_PD1-S2_scRNA OEX021096 OES287042 6 2023-02-16 OER378559 YAK_Anakinra_PD1-S3_scRNA OEX021096 OES287043 4 2023-02-16 OER378560 YAK_IL1RN-201-S1_scRNA OEX021096 OES287023 2 2023-02-16 OER378561 YAK_IL1RN-201-S2_scRNA OEX021096 OES287024 2 2023-02-16 OER378562 YAK_IL1RN-201-S3_scRNA OEX021096 OES287025 2 2023-02-16 OER378563 YAK_IL1RN-203-S1_scRNA OEX021096 OES287026 4 2023-02-16 OER378564 YAK_IL1RN-203-S2_scRNA OEX021096 OES287027 2 2023-02-16 OER378565 YAK_IL1RN-203-S3_scRNA OEX021096 OES287028 6 2023-02-16 OER378566 YAK_Vector_Anakinra-S1_scRNA OEX021096 OES287038 2 2023-02-16 OER378567 YAK_Vector_Anakinra-S2_scRNA OEX021096 OES287039 2 2023-02-16 OER378568 YAK_Vector_Anakinra-S3_scRNA OEX021096 OES287040 2 2023-02-16 OER378569 YA_IgG-S1_scRNA OEX021096 OES287044 4 2023-02-16 OER378570 YA_IgG-S2_scRNA OEX021096 OES287045 2 2023-02-16 OER378571 YA_IgG-S3_scRNA OEX021096 OES287046 2 2023-02-16 OER378572 YA_PD1-S1_scRNA OEX021096 OES287047 2 2023-02-16 OER378573 YA_PD1-S2_scRNA OEX021096 OES287048 2 2023-02-16 OER378574 YA_PD1-S3_scRNA OEX021096 OES287049 4 2023-02-16 OER378765 YA-1-1_RNASeq OEX021331 OES287008 1 2023-02-21 OER378766 YA-1-2_RNASeq OEX021331 OES287008 1 2023-02-21 OER378767 YA-2-1_RNASeq OEX021331 OES287009 1 2023-02-21 OER378768 YA-2-2_RNASeq OEX021331 OES287009 1 2023-02-21 OER378769 YA-3-1_RNASeq OEX021331 OES287010 1 2023-02-21 OER378770 YA-3-2_RNASeq OEX021331 OES287010 1 2023-02-21 OER378771 YA-4-1_RNASeq OEX021331 OES287011 1 2023-02-21 OER378772 YA-4-2_RNASeq OEX021331 OES287011 1 2023-02-21 OER378773 YA-5-1_RNASeq OEX021331 OES287012 1 2023-02-21 OER378774 YA-5-2_RNASeq OEX021331 OES287012 1 2023-02-21 OER378775 YA-6-1_RNASeq OEX021331 OES287013 1 2023-02-21 OER378776 YA-6-2_RNASeq OEX021331 OES287013 1 2023-02-21 OER378777 YAK-1-1_RNASeq OEX021331 OES287014 1 2023-02-21 OER378778 YAK-1-2_RNASeq OEX021331 OES287014 1 2023-02-21 OER378779 YAK-2-1_RNASeq OEX021331 OES287015 1 2023-02-21 OER378780 YAK-2-2_RNASeq OEX021331 OES287015 1 2023-02-21 OER378781 YAK-3-1_RNASeq OEX021331 OES287016 1 2023-02-21 OER378782 YAK-3-2_RNASeq OEX021331 OES287016 1 2023-02-21 OER378783 YAK-4-1_RNASeq OEX021331 OES287017 1 2023-02-21 OER378784 YAK-4-2_RNASeq OEX021331 OES287017 1 2023-02-21 OER378785 YAK-5-1_RNASeq OEX021331 OES287018 1 2023-02-21 OER378786 YAK-5-2_RNASeq OEX021331 OES287018 1 2023-02-21 OER378787 YAK-6-1_RNASeq OEX021331 OES287019 1 2023-02-21 OER378788 YAK-6-2_RNASeq OEX021331 OES287019 1 2023-02-21 - Analysis
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1
Analysis ID Analysis Title Analysis Type Data Date OEZ013253 Single cell gene_expression Other 30 2023-02-16
Author Information
- Create Date
- 2022-11-20
- Last Modified
- 2023-07-27
- Submission
- Mao Zhang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital