mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell Carcinoma.
Am J Pathol
; 191(11): 1999-2008, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34358517
ABSTRACT
The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Regulação Neoplásica da Expressão Gênica
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Serina-Treonina Quinases TOR
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Antígeno B7-H1
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Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2021
Tipo de documento:
Article