ArticleJournal of cellular and molecular medicine2020
TFE3-PD-L1 axis is pivotal for sunitinib resistance in clear cell renal cell carcinoma.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Trends and hotspots in targeted therapy resistance research for renal cell carcinoma: a bibliometric and visualization analysis.Discover oncology · 2025Article
- Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the "all-around warrior" in immunotherapy.Molecular cancer · 2024Review
- PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Molecular cancer · 2024Review
- Molecular and functional characterization of reversible-sunitinib-tolerance state in human renal cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Treatment of metastatic TFE3 microphthalmia transcription factor translocation renal cell carcinoma: a case report.Translational pediatrics · 2024Article
- TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma.Heliyon · 2023Article
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- TFE3-PD-L1 axis is pivotal for sunitinib resistance in clear cell renal cell carcinoma.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The microphthalmia of bHLH-LZ transcription factor (MiT/TFE) family chromosomal translocation or overexpression is linked with a poor prognosis in clear cell renal cell carcinoma (ccRCC) with elevated recurrence and drug resistance, but the molecular mechanism is not fully understood. Here, we investigated whether the resistance to sunitinib (Sun), the standard treatment for metastatic ccRCC, is due to up-regulation of programmed death ligand 1 (PD-L1) by the transcription factor E3 (TFE3). In this study, we propose that TFE3 but not TFEB is essential for tumour survival which was associated with the poorer survival of cancer patients. We also found a positive correlation between TFE3 and PD-L1 expression in ccRCC cells and tissues. Sun treatment led to enhanced TFE3 nuclear translocation and PD-L1 expression. Finally, we observed the therapeutic benefit of Sun plus PD-L1 inhibition which enhanced CD8+ cytolytic activity and thus tumour suppression in a xenografted mouse model. These data revealed that TFE3 is a potent tumour promoting gene and it mediates resistance to Sun by induction of PD-L1 in ccRCC. Our data provide a strong rationale to apply Sun and PD-L1 inhibition jointly as a novel immunotherapeutic approach for ccRCC treatment.
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