• Title/Summary/Keyword: PD-L2

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Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)

  • Nam, Sorim;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.63-70
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    • 2019
  • Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

Predictions of PD-L1 Expression Based on CT Imaging Features in Lung Squamous Cell Carcinoma (편평세포폐암에서 CT 영상 소견을 이용한 PD-L1 발현 예측)

  • Seong Hee Yeo;Hyun Jung Yoon;Injoong Kim;Yeo Jin Kim;Young Lee;Yoon Ki Cha;So Hyeon Bak
    • Journal of the Korean Society of Radiology
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    • v.85 no.2
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    • pp.394-408
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    • 2024
  • Purpose To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. Materials and Methods A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Results For the total patient group, the AUC of the 'total significant features model' (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the 'selected feature model' (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the 'selected feature model' (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Conclusion Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1.

Novel Linking Ligand Containing Sulfur-Donor Atoms and Its Compounds of Palladium and Silver

  • Lee, Hee-K.;Lee, Soon-W.
    • Bulletin of the Korean Chemical Society
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    • v.28 no.3
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    • pp.421-426
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    • 2007
  • A linking ligand containing sulfur donor atoms in the terminal thiophene rings, 1,2-bis(thiophen-2-ylmethylene) hydrazine (L), was prepared by Schiff-base condensation. Ligand L reacted with [PdCl2(NCPh)2] to produce a molecular Pd compound [PdL2Cl2] (1). On the other hand, it reacted with AgNO3 and AgClO4 to produce a 2-D network [AgL0.5(NO3)] (2) and a 1-D polymer [AgL]ClO4 (3), respectively, whose structures are based on secondary intermolecular forces such as H-bonding, van der Waals interaction, and π-π stacking. Polymer 2 exhibited photoluminescence at room temperature in the solid state.

The Activation of HCV-specific CD8 T Cells by HCV Peptide Pulsed Huh7.5 Cells (Huh7.5 간암 세포주의 HCV 항원제시에 의한 HCV 특이 T 림프구의 활성에 관한 연구)

  • Cho, Hyo-Sun
    • Korean Journal of Microbiology
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    • v.47 no.4
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    • pp.342-347
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    • 2011
  • T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

First Example of Monometallic Palladium(II) Compound with Trans-Chelating Tridentate Ligand: Synthesis, Crystal Structure, and Characterizations

  • Tae Hwan Noh
    • Mass Spectrometry Letters
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    • v.14 no.3
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    • pp.110-115
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    • 2023
  • The reaction of (COD)PdCl2 with new C3-symmetric tridentate L (COD = 1,5-cyclooctadien; L = 1,3,5-tris(picolinoyloxyethyl)cyanurate) in a mixture of acetone and dichloromethane produces single crystals consisting of unprecedented monometallacyclic [PdCl2(L)]. This cyclic compound arises from trans-chelation of two of three donating pyridyl groups of L, while the third pyridyl group remains uncoordinated. Electrospray ionization mass spectrometry (ESI-MS) data on L exhibited the major peak corresponding to [C27H24N6O9 + H+]+. Fast atom bombardment mass spectrometry (FABMS) data on [PdCl2(L)], however, showed the mass peak corresponding to the L instead of the present palladium(II) compound species, due to the insolubility and dissociation in solution. The physicochemical properties of the present palladium(II) compound were fully characterized by means of infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy, thermal analysis, single-crystal X-ray diffraction (SC-XRD) measurement.

Preparation of Pd/Al2O3, Pd/Ag/Al2O3 Membranes and Evaluation of Hydrogen Permeation Performance (Pd/Al2O3, Pd/Ag/Al2O3 분리막의 제조와 수소 투과 성능 평가)

  • Lee, Jeong In;Shin, Min Chang;Zhuang, Xuelong;Hwang, Jae Yeon;Kim, Eok yong;Jeong, Chang-Hun;Park, Jung Hoon
    • Membrane Journal
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    • v.32 no.2
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    • pp.116-125
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    • 2022
  • In this experiment, an α-Al2O3 ceramic hollow fiber was used as a support, and a hydrogen membrane plated with Pd and Pd-Ag was manufactured through electroless plating. The Pd-Ag membrane was annealed at 500℃ for 10 h to form an alloy of Pd and Ag. It was confirmed that it became a Pd-Ag alloy through EDS (Energy Dispersive X-ray Spectroscopy) analysis. Also, the thickness of the Pd, Pd-Ag plating layer was measured to be about 8.98 and 9.29 ㎛ through SEM (Scanning Electron Microscope) analysis respectively. Hydrogen permeation experiment was performed using the H2 gas and mixed gas (H2 and N2) in the range of 350~450℃ and 1-4 bar using the prepared hydrogen membrane. Under the H2 gas condition, the Pd and Pd-Ag membrane has a flux of up to 21.85 and 13.76 mL/cm2·min and also separation factors of 1216 and 361 were obtained in the mixed gas at 450℃ and 4 bar conditions respectively.

Biological production of 1,3-propanediol using crude glycerol derived from biodiesel process (바이오디젤 부산물인 폐글리세롤을 이용한 생물학적 1,3-propanediol 생산)

  • Jun, Sun-Ae;Kang, Cheol-Hee;Kong, Sean-W.;Sang, Byoung-In;Um, Young-Soon
    • KSBB Journal
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    • v.23 no.5
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    • pp.413-418
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    • 2008
  • The production of 1,3.propanediol (1,3-PD) was investigated with Klebsiella pneumoniae DSM2026 and K. pneumoniae DSM4799 using crude glycerol obtained from biodiesel industry. Crude glycerol was used without prior purification to investigate effects of impurities in crude glycerol on 1,3-PD production. In the batch cultures, 1,3-PD production with crude glycerol was $1.1{\sim}2.5$ times higher than that with pure glycerol, indicating that crude glycerol is even a better substrate than pure glycerol for 1,3-PD fermentation. When glucose was added, 1,3-PD production and yield decreased in spite of enhanced cell growth. Furthermore, the addition of glucose was found to increase 2,3-butanediol, a by-product, significantly because of the change in metabolism in the presence of glucose. In semi-batch cultures without glucose addition, 26 g/L 1,3-PD was produced with crude glycerol, which was $2{\sim}3$ times higher than that with pure glycerol. Based on our results, it was clearly shown that crude glycerol is an effective substrate for biological 1,3-PD production, making it more feasible to produce 1,3-PD at a lower price.

Effects of Ni Addition on the Microstructures and Magnetic Properties of Fe70-xPd30Nix High-Temperature Ferromagnetic Shape Memory Alloys

  • Lin, Chien-Feng;Yang, Jin-Bin
    • Journal of Magnetics
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    • v.17 no.2
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    • pp.86-95
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    • 2012
  • This study investigated the effects of adding a third alloying element, Ni, to create $Fe_{70-x}Pd_{30}Ni_x$ (x = 2, 4, 6, 8 at.% Ni) ferromagnetic shape memory alloys (FSMAs). The Ni replaced a portion of the Fe. The $Fe_{70-x}Pd_{30}Ni_x$ alloys were homogenized through hot and cold forging to gain a ~38% reduction in thickness, next they were solution-treated (ST) with annealing recrystallization at $1100^{\circ}C$ for 8 h and quenched in ice brine, and then aged at $500^{\circ}C$ for 100 h. Investigation of the microstructures and magnetostriction indicated that the greater Ni amount in the $Fe_{70-x}Pd_{30}Ni_x$ alloys reduced saturation magnetostriction at room temperature (RT). It was also observed that it was more difficult to generate annealed recrystallization. However, with greater Ni addition into the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys, the $L1_0+L1_m$ twin phase decomposition into stoichiometric $L1_0+L1_m+{\alpha}_{bct}$ structures was suppressed after the $500^{\circ}C$/100 h aging treatment. The result was that the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys maintained a high magnetostriction and magnetostrictive susceptibility (${\Delta}{\lambda}{_\parallel}{^s}/{\Delta}H$) after the alloys were aged at $500^{\circ}C$ for 100 h. This magnetic property of the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys make it suitable for application in a high temperature (T > $500^{\circ}C$) and high frequency environments.

1,3-Propanediol Fermentation using the by-Products from Fat Industry (글리세롤을 함유한 유지산업 부산물의 1,3-propanediol 발효)

  • 김철호;김승환;김세정;박건규;이상기
    • KSBB Journal
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    • v.17 no.3
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    • pp.255-260
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    • 2002
  • 1,3-Propanediol as a bifunctional organic compound could be used in polymerization reactions producing polyesters and polyurethanes. Byproduct containing high concentration of glycerol from fat industry was used to produce 1,3-propanediol in lower production cost as well as waste treatment. In this study, various attempts were made to increase 1,3-propanediol production under different conditions using Klebsiella pneumoniae ATCC 15380. The conversion yield and byproduct formation were influenced significantly by the fermentation pH and temperature. The optimal glycerol and nitrogen concentration for 1,3-propanediol production were found to be 25 a/L and 1%(w/v), respectively. The formation of 1,3-propanediol was optimal at pH 6.0 and temperature $35^{\circ}C$. 1,3-Propanediol production from byproduct from 2.5% glycerol was lower than that of 2.5% commercial glycerol and amounted only to 9.84 a/L from byproduct, while to 12.13 a/L from commercial glycerol.