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Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Lim, Jongchul,Kim, Taewan,Park, Taiho The Royal Society of Chemistry 2014 ENERGY AND ENVIRONMENTAL SCIENCE Vol.7 No.12
<P>We report a novel way to accelerate the rate of oxidized sensitizer neutralization on nanocrystalline TiO<SUB>2</SUB> electrode surfaces using a novel coadsorbent, 3,4,5-tris-butenyloxy benzoic acid (<B>TD</B>), having three terminal double bonds. <SUP>1</SUP>H NMR and contact angle measurements revealed that the terminal double bonds reacted with I<SUB>2</SUB> to form an <I>in situ</I>-generated ionic layer of I<SUP>−</SUP> species. Transient absorption spectroscopy (TAS) and electrochemical impedance spectroscopy (EIS) studies demonstrated that I<SUP>−</SUP> species neighbouring the cationic dye molecules (D<SUP>+</SUP>) accelerate the neutralization (or regeneration) rate (<I>k</I><SUB>D<SUP>+</SUP></SUB>), as well as decrease the recombination reactions of photoinduced electrons with D<SUP>+</SUP> (<I>k</I><SUB>1</SUB>) and I<SUB>3</SUB><SUP>−</SUP> (<I>k</I><SUB>2</SUB>). Dye-sensitized solar cells treated with <B>TD</B> exhibit a power conversion efficiency of 10.2%, which is 22% higher due to the simultaneous improvements in <I>J</I><SUB>SC</SUB> and <I>V</I><SUB>OC</SUB>, even at 15% low dye loading levels, compared to the values obtained from a conventional device.</P> <P>Graphic Abstract</P><P>A novel coadsorbent including three terminal double bonds reacted with I<SUB>2</SUB> and generated ionic complexes on the surface of TiO<SUB>2</SUB>. The <I>in situ</I>-generated ionic layer accelerated the neutralization rate of dye<SUP>+</SUP> and decreased the recombination reactions with dye<SUP>+</SUP> and I<SUB>3</SUB><SUP>−</SUP> due to coadsorbent effects, resulting in 22% higher power conversion efficiency, even at 15% low dye loading, compared to the conventional device. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4ee01950d'> </P>