2022
DOI: 10.1186/s13046-022-02253-0
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A novel FBW7/NFAT1 axis regulates cancer immunity in sunitinib-resistant renal cancer by inducing PD-L1 expression

Abstract: Background Tyrosine kinase inhibitors (TKIs) alone and in combination with immune checkpoint inhibitors (ICIs) have been shown to be beneficial for the survival of metastatic renal cell carcinoma (mRCC) patients, but resistance to targeted therapy and ICIs is common in the clinic. Understanding the underlying mechanism is critical for further prolonging the survival of renal cancer patients. Nuclear factor of activated T cell 1 (NFAT1) is expressed in immune and nonimmune cells, and the dysregu… Show more

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Cited by 26 publications
(12 citation statements)
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References 68 publications
(72 reference statements)
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“…Silencing FOXA1 or FOXD1 in RCC inhibits tumor growth by inhibiting cell cycle progression [ 31 , 32 ]. Moreover, recent research has indicated that FOXA1 may participate in sunitinib resistance in RCC [ 33 ]. Several studies have confirmed the vital role of FOXM1, which may serve as an essential prognostic biomarker and therapeutic target for renal cancer.…”
Section: Discussionmentioning
confidence: 99%
“…Silencing FOXA1 or FOXD1 in RCC inhibits tumor growth by inhibiting cell cycle progression [ 31 , 32 ]. Moreover, recent research has indicated that FOXA1 may participate in sunitinib resistance in RCC [ 33 ]. Several studies have confirmed the vital role of FOXM1, which may serve as an essential prognostic biomarker and therapeutic target for renal cancer.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, these patients with SETD2 mutated cancer were accompanied by transcriptional upregulation of genes associated with immune activity (46). Another clinical analysis of lung adenocarcinoma found many SETD2 gene mutations and significantly higher IFNg expression in the PD-L1 high-expression group (47). Furthermore, an experimental study in renal cell carcinoma found that SETD2 acts as a transcription factor regulating E3 ubiquitin ligase FBW7 target gene expression, causing altered PD-L1 expression levels and promoting CD4 + and CD8 + T cell infiltration and enhancing the anti-tumor effects of PD-1 antibodies (48).…”
Section: Setd2mentioning
confidence: 99%
“…Another clinical analysis of lung adenocarcinoma found many SETD2 gene mutations and significantly higher IFN-γ expression in the PD-L1 high-expression group ( 47 ). Furthermore, an experimental study in renal cell carcinoma found that SETD2 acts as a transcription factor regulating E3 ubiquitin ligase FBW7 target gene expression, causing altered PD-L1 expression levels and promoting CD4 + and CD8 + T cell infiltration and enhancing the anti-tumor effects of PD-1 antibodies ( 48 ). Based on the above studies, mutations in SETD2 are significantly correlated with tumor immune-specific genes and can drive tumor immunophenotypic alterations.…”
Section: Classification and Biological Functions Of Histone Methyltra...mentioning
confidence: 99%
“…The high expression of Nuclear Factors of Activated T-cell (NFAT) is a common feature of many human cancers, and it has been linked to tumor growth, sunitinib resistance, and improved PD-L1 expression via the PI3K/AKT/GSK-3β signaling pathway ( 27 ). FBXW7 induces NFAT1 degradation, leading to PD-L1 downregulation and subsequent immunoreaction, which is correlated with prognosis ( 28 ).…”
Section: Fbxw7 Ubiquitinates Its Downstream Substrates To Regulate Dr...mentioning
confidence: 99%