Academic Journal
PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI-Resistant Metastatic Clear Cell Renal Cell Carcinoma
| العنوان: | PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI-Resistant Metastatic Clear Cell Renal Cell Carcinoma |
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| المساهمون: | Se Un Jeong, Hee Sang Hwang, Ja-Min Park, Sun Young Yoon, Su-Jin Shin, Heounjeong Go, Jae-Lyun Lee, Gowun Jeong, Yong Mee Cho, Shin, Su Jin |
| بيانات النشر: | Official journal of Korean Cancer Association |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | B7-H1 Antigen / metabolism, Carcinoma, Renal Cell* / drug therapy, Renal Cell* / genetics, Renal Cell* / pathology, Humans, Kidney Neoplasms* / drug therapy, Kidney Neoplasms* / genetics, Kidney Neoplasms* / metabolism, Protein Kinase Inhibitors / pharmacology, Protein Kinase Inhibitors / therapeutic use, Receptor Protein-Tyrosine Kinases / genetics, TOR Serine-Threonine Kinases / metabolism, Up-Regulation, Vascular Endothelial Growth Factor A / metabolism, B7-H1 antigen, Receptor protein-tyrosine kinases, Renal cell carcinoma, TOR serine-threonine kinases |
| الوصف: | Purpose: Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism. Materials and methods: To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib. Results: Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway. Conclusion: These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI-resistant mCCRCC patients via the mTOR pathway. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English Korean |
| تدمد: | 1598-2998 2005-9256 |
| Relation: | CANCER RESEARCH AND TREATMENT; J00453; OAK-2022-11163; https://ir.ymlib.yonsei.ac.kr/handle/22282913/193644; T202301274; CANCER RESEARCH AND TREATMENT, Vol.55(1) : 231-244, 2023-01 |
| DOI: | 10.4143/crt.2021.1526 |
| الاتاحة: | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193644 https://doi.org/10.4143/crt.2021.1526 |
| Rights: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.80BC9D18 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15982998 20059256 |
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| DOI: | 10.4143/crt.2021.1526 |