• IMMUNE NETWORK
• /
• v.20 no.1
• /
• pp.8.1-8.15
• /
• 2020

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

• IMMUNE NETWORK
• /
• v.16 no.2
• /
• pp.134-139
• /
• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• Journal of the Korean Vacuum Society
• /
• v.6 no.2
• /
• pp.165-171
• /
• 1997

If the thickness of Pd deposited is larger than 9$\AA$, its phase is $Pd_3Si$. This phase is followed by pure Pd phase with further deposition of Pd. Also, when the thickness of Pd deposited on top of Si(111) is larger than 1$\AA$, the phase of Pd-silicide formed is found to be Pd2Si. The full width at half maximum of Pd 3d core-levels increases with decreasing of Pd film thickness at low coverages ($\leq0.5\AA$). This is due to the formation of additional phase of Pd silicide, i.e. PdSi, in addition to $Pd_2Si$.

• Bulletin of the Korean Chemical Society
• /
• v.23 no.12
• /
• pp.1754-1758
• /
• 2002

Tetrathiafulvalene(TTF) reacts with $PdCl_2,Pd(NO_3)_2$ and $Pd(hfacac)_2$(hexafluoroacetylacetonate) in ethanol to give $(TTF)_{1.5}PdCl_2$ (1a), $(TTF)_3Pd(NO_3)_2$ (1b) and $(TTF)_4Pd(hfacas)_2$ nd (1c), respectively. $PdCl(TCNQ)_{2.5}{\cdot}CH_3OH(2a)$was obtained from the reaction of $PdCl_2$ with LiTCNQ in methanol via the partial replacement of $Cl^-$ in $PdCl_2$ by $TCNQ^-$anion, whereas the total substitution of the labile $NO_3^-$ in $Pd(NO_3)_2$ yielded pd(TCNQ)·$CH_3OH$ (2b). $Pd(hfacac)_2(TCNQ)_2\cdot3CH_3OH$ (2c) was obtained from $Pd(hfacac)_2$ and LiTCNQ in methanol. The prepared compounds were characterized by spectroscopic (IR, UV, XPS) methods and magnetic (EPR, magnetic susceptibility) studies. The powdered electrical conductivities (${\sigma}_{rt}$) of the prepared compounds at room temperature were about~$10^{-7}S{\cdot}cm^{-1}$. The effective magnetic moments were lass than the spin-only value of one unpaired electron and no EPR signals from Pd metal ions were observed in any of the compounds, indicating that the Pd ions were diamagnetic and the magnetic moments arose from$(TTF)_n$ or $(TCNQ)_n$ moieties. The experimental evidences revealed that the charge transfer had occurred form $(TTF)_n$ moiety to the central Pd metal ion in 1a, 1b and 1c. Thus the TTF donors were ions in 2a and 2b were diamagnetic Pd(II) oxidation state. In contrast, the Pd metal ion was oxidized to Pd(IV) state in 2c as a result of an addition of $TCNQ^-$anion to $Pd(hfacac)_2$ in methanol. The oxidation states of the Pd metal ions were confirmed using the x-ray photoelectron spectroscopy.

• Korean Journal of Microbiology
• /
• v.49 no.4
• /
• pp.301-308
• /
• 2013

Programmed Death-1 (PD-1) is one of the important immune-inhibitory molecules which was expressed in T cells, B cells, NKT cells, and macrophages activated by various immune activating factors. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is one of the crucial immunogens for PD-1 expression. However, there are only a few reports on the expression mechanisms of PD-1 in innate immune cells. In this study, we investigate the expression mechanisms of PD-1 in LPS-stimulated Raw264.7 cell lines by RT-PCR, Western Blot, flow cytometry as well as ChIP assay and co-immunoprecipitation. When Raw264.7 cells were stimulated with LPS, PD-1 expression was greatly up-regulated via PI3K and p38 signaling. Primary macrophages isolated from LPS-injected mice were also shown the increased expression of PD-1. In promoter assay, NF-${\kappa}B$ and IRF-1 binding regions in mouse PD-1 promoter are important for PD-1 expression. We also found that the co-activation of NF-${\kappa}B$ and IRF-1 is indispensable for the maximum PD-1 expression. These results indicate that the modulation of PD-1 expressed in innate immune cells could be a crucial for the disease therapy such as LPS-induced mouse sepsis model.

• 한국전기화학회:학술대회논문집
• /
• 2002.07a
• /
• pp.211-218
• /
• 2002

In this study, Pt/Pd (1.1), PtPd (2:1) and PtPd (3:1) binary catalysts and Pt/Ru/Pd (5:4:1) ternary catalyst were designed. The catalysts were synthesized by impregnation method using $NaBH_4$ as a reducing agent. A good catalyst for methanol oxidation requires low on-set potential, stable durability and low activation energy. In order to investigate the catalytic activity for the methanol oxidation, electrochemical measurements such as cyclic voltammetry and chronoamperometry were peformed in sulfuric acid with/without methanol solution. In order to calculate the activation energy of the reaction, electrochemical measurements were also tested at different temperatures. For investigation of the structural analysis such as particle size and alloying, X-ray diffraction and transmission electron microscopy analysis were used. In order to identify the role of the Pd and to determine the composition of the surface of the Pt/Pd nanoparticles, X-ray photoelectron spectroscopy (XPS) analysis was investigated. The XPS spectra of Pd showed that Pd appears only as a metallic state in the binary catalysts. The chemical states of Pt in PtPd catalysts are both metallic and oxidative. Polarization curves and power density data were obtained by testing the DMFC unit cell performance of PtPd and PtRuPd catalysts. These data showed that Pt/Pd (2:1) and Pt/Ru/Pd (5:4:1) have better performance than Pt and Pt/Ru, respectively.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.4
• /
• pp.343-350
• /
• 2008

PD-L1 is expressed in a variety of antigen-presenting cells and provides T cell tolerance via ligation with its receptor PD-1 and B7-1 on T cells. Stimulation with lipopolysaccharide (LPS) can increase the level of PD-L1 expression in B cells and macrophages, which suggests that this molecule plays a role in the immunosuppression observed in severe sepsis. The aim of this study was to identify which of the downstream pathways of TLR4 are involved in the up-regulation of PD-L1 by LPS in macrophages. Flow cytometry was used to examine the expression of PD-L1 in RAW 264.7 macrophages stimulated with LPS. The following chemical inhibitors were used to evaluate the role of each pathway: LY294002 for PI3K/Akt, SB202190 for p38 MAPK, and U0126 for MEK. LPS induced the expression of PD-L1 in a time- and dose-dependent manner. Transfection of siRNA for TLR4 suppressed the induction of PD-L1. Pretreatment with LY294002 and SB202190 decreased the level of PD-L1 expression but U0126 did not. Overall, the PI3K/Akt and p38 MAPK pathways are involved in the up-regulation of PD-L1 expression in RAW 264.7 macrophages stimulated with LPS.

• Biomolecules & Therapeutics
• /
• v.27 no.1
• /
• pp.63-70
• /
• 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.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
• /
• v.16 no.8
• /
• pp.744-751
• /
• 2003

Co-Pd alloy thin films prepared by a DC-sputter that have self-organized nano structure(SONS), are promising for high-density information storage media in information era. We prepared the samples by varying Pd contents of 0~8.1 wt% at the substrate temperatures of room temperature (RT) and 200 $^{\circ}C$, respectively Microstructure and Pd contents of the Co$_{1-x}$ Pd$_{x}$ films are probed by a scanning electron microscope (SEM), a transmission electron microscope (TEM) and an energy dispersive spectrometer (EDS). We also investigated the saturation magnetization (Ms), remanence and coercivity of the Co$_{1-x}$ Pd$_{x}$ films. Surface roughness are measured by an atomic force microscope (AFM). We revealed that self-organized nano size Co-enriched phase and Pd-enriched phase existed with Pd contents at the substrate temperatures of RT and 20$0^{\circ}C$ through microstructure characterization. SONS helped to keep the saturation magnetization and enhance the perpendicular anisotropy with Pd contents. Out result implies that we may tune the perpendicular magnetic properties with keeping the saturation magnetization by varying substrate temperatures and Pd contents for high density magnetic recording.rding.

• Journal of Veterinary Science
• /
• v.22 no.5
• /
• pp.75.1-75.10
• /
• 2021

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. Objectives: This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. Methods: Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2-3.7] ng/mL; median [IQR] and 2.4 [1.4-4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9-3.0] ng/mL; p = 0.012 and 1.4 [0.9-2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9-3.0] ng/mL and 3.1 [2.6-4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9-2.1] ng/mL and 2.7 [1.6-5.8] ng/mL, respectively; p < 0.001). Conclusion: This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.