PMID- 34358517
OWN - NLM
STAT- MEDLINE
DCOM- 20211105
LR  - 20211204
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 191
IP  - 11
DP  - 2021 Nov
TI  - mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates 
      Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell 
      Carcinoma.
PG  - 1999-2008
LID - S0002-9440(21)00344-8 [pii]
LID - 10.1016/j.ajpath.2021.07.007 [doi]
AB  - 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.
CI  - Copyright (c) 2021 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Lee, Hyun Jung
AU  - Lee HJ
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea; The Research Institute for Convergence of Biomedical Science 
      and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of 
      Korea.
FAU - Shin, Dong Hoon
AU  - Shin DH
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea; The Research Institute for Convergence of Biomedical Science 
      and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of 
      Korea. Electronic address: donghshin@pusan.ac.kr.
FAU - Song, Ji Sun
AU  - Song JS
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Park, Joon Young
AU  - Park JY
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Kim, So Young
AU  - Kim SY
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Hwang, Chung Su
AU  - Hwang CS
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Na, Ju-Young
AU  - Na JY
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Lee, Jung Hee
AU  - Lee JH
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Kim, Jee Yeon
AU  - Kim JY
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Park, Sung Woo
AU  - Park SW
AD  - Department of Urology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
FAU - Sol, Mee Young
AU  - Sol MY
AD  - Department of Pathology, School of Medicine, Pusan National University, Yangsan, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210804
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (TFE3 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - B7-H1 Antigen/*metabolism
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism
MH  - Carcinoma, Renal Cell/*metabolism
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Humans
MH  - Kidney Neoplasms/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2021/08/07 06:00
MHDA- 2021/11/06 06:00
CRDT- 2021/08/06 20:10
PHST- 2021/04/14 00:00 [received]
PHST- 2021/06/13 00:00 [revised]
PHST- 2021/07/02 00:00 [accepted]
PHST- 2021/08/07 06:00 [pubmed]
PHST- 2021/11/06 06:00 [medline]
PHST- 2021/08/06 20:10 [entrez]
AID - S0002-9440(21)00344-8 [pii]
AID - 10.1016/j.ajpath.2021.07.007 [doi]
PST - ppublish
SO  - Am J Pathol. 2021 Nov;191(11):1999-2008. doi: 10.1016/j.ajpath.2021.07.007. Epub 
      2021 Aug 4.