Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors
Summary: The evolutionarily conserved Notch pathway, involved in cancer stem cell capacity and cancer immunity, may predict the benefit from immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). In the TCGA dataset, mRNA expression of Notch pathway genes identified three cl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223023672 |
| _version_ | 1797388757953937408 |
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| author | Sujun Han Yu Xu Dong Chen Feiya Yang Mingshuai Wang Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Nianzeng Xing |
| author_facet | Sujun Han Yu Xu Dong Chen Feiya Yang Mingshuai Wang Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Nianzeng Xing |
| author_sort | Sujun Han |
| collection | DOAJ |
| description | Summary: The evolutionarily conserved Notch pathway, involved in cancer stem cell capacity and cancer immunity, may predict the benefit from immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). In the TCGA dataset, mRNA expression of Notch pathway genes identified three clusters with different prognoses and molecular characteristics. Based on the differentially expressed Notch pathway genes between clusters, we constructed the Notch-score, correlated with Notch activation, angiogenesis, PI3K-AKT-mTOR activity, and sensitivities to VEGFR/mTOR inhibitors. A high Notch-score was linked with more “resting”/“anti-inflammatory” rather than “activated”/“pro-inflammatory” tumor-infiltrating immune cells, inactivated immune pathways, and scarce any benefits from ICI-based therapies over VEGFR/mTOR inhibitors in the JAVELIN Renal 101 (avelumab plus axitinib vs. sunitinib) and the CheckMate-009/010/025 trials (nivolumab vs. everolimus). For the Notch-activated ccRCCs, ICIs provide limited advantages and might not be strongly recommended, by which the cost-effectiveness of treatments in ccRCCs may be potentially improved. |
| first_indexed | 2024-03-08T22:45:27Z |
| format | Article |
| id | doaj.art-9f0b266ea75c42bd9eab268846484edc |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:27Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9f0b266ea75c42bd9eab268846484edc2023-12-17T06:40:22ZengElsevieriScience2589-00422024-01-01271108290Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitorsSujun Han0Yu Xu1Dong Chen2Feiya Yang3Mingshuai Wang4Qiaoxia Zhou5Guoqiang Wang6Leo Li7Chunwei Xu8Wenxian Wang9Shangli Cai10Nianzeng Xing11Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBurning Rock Biotech, Guangzhou, Guangdong, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBurning Rock Biotech, Guangzhou, Guangdong, ChinaBurning Rock Biotech, Guangzhou, Guangdong, ChinaBurning Rock Biotech, Guangzhou, Guangdong, ChinaInstitute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, ChinaDepartment of Clinical Trial, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, ChinaBurning Rock Biotech, Guangzhou, Guangdong, ChinaDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China; Corresponding authorSummary: The evolutionarily conserved Notch pathway, involved in cancer stem cell capacity and cancer immunity, may predict the benefit from immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). In the TCGA dataset, mRNA expression of Notch pathway genes identified three clusters with different prognoses and molecular characteristics. Based on the differentially expressed Notch pathway genes between clusters, we constructed the Notch-score, correlated with Notch activation, angiogenesis, PI3K-AKT-mTOR activity, and sensitivities to VEGFR/mTOR inhibitors. A high Notch-score was linked with more “resting”/“anti-inflammatory” rather than “activated”/“pro-inflammatory” tumor-infiltrating immune cells, inactivated immune pathways, and scarce any benefits from ICI-based therapies over VEGFR/mTOR inhibitors in the JAVELIN Renal 101 (avelumab plus axitinib vs. sunitinib) and the CheckMate-009/010/025 trials (nivolumab vs. everolimus). For the Notch-activated ccRCCs, ICIs provide limited advantages and might not be strongly recommended, by which the cost-effectiveness of treatments in ccRCCs may be potentially improved.http://www.sciencedirect.com/science/article/pii/S2589004223023672Health sciencesGene ontologyMolecular biologyImmunologyCancerTranscriptomics |
| spellingShingle | Sujun Han Yu Xu Dong Chen Feiya Yang Mingshuai Wang Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Nianzeng Xing Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors iScience Health sciences Gene ontology Molecular biology Immunology Cancer Transcriptomics |
| title | Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors |
| title_full | Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors |
| title_fullStr | Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors |
| title_full_unstemmed | Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors |
| title_short | Notch activation defines immune-suppressive subsets of ccRCCs with unfavorable benefits from immunotherapy over VEGFR/mTOR inhibitors |
| title_sort | notch activation defines immune suppressive subsets of ccrccs with unfavorable benefits from immunotherapy over vegfr mtor inhibitors |
| topic | Health sciences Gene ontology Molecular biology Immunology Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223023672 |
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