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https://www.readbyqxmd.com/read/28332100/expression-of-programmed-death-1-and-its-ligands-in-the-liver-of-biliary-atresia
#1
Pan-Liang Wang, Jun Wang, Ying Zhou, Xiao-Song Chen, Ke-Jun Zhou, Jie Wen, Jian-Jun Zhang, Wei Cai
BACKGROUND: An aberrant immune response is the predominant pathogenetic factor in biliary atresia (BA). Programmed death-1 (PD-1) and its two ligands, programmed death ligand-1 and programmed death ligand-2 (PD-L1 and PD-L2, respectively) play an important inhibitory role in immune reactions. We aimed to illustrate the expression of these molecules in BA. METHODS: Liver specimens were obtained from infants with BA during the Kasai procedure (early BA) and liver transplantation (late BA)...
March 22, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#2
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28314313/pd-l1-expression-confers-better-prognosis-in-locally-advanced-oral-squamous-cell-carcinoma
#3
Yasunao Kogashiwa, Masanori Yasuda, Hiroyuki Sakurai, Mitsuhiko Nakahira, Yoshie Sano, Kenji Gonda, Tetsuya Ikeda, Hitoshi Inoue, Kiyomi Kuba, Susumu Oba, Junichi Ishikawa, Yuichiro Enoki, Satoko Matsumura, Kazuhiko Minami, Yasuhiro Ebihara, Masashi Sugasawa
BACKGROUND/AIM: Clinical trials with therapies targeting immune checkpoint molecules have shown promising results in several tumor types. However, the predictive and prognostic values of these immunological factors for locally advanced oral squamous cell carcinomas (LAOSCC) remain unclear. Our purpose was to evaluate the expression and prognostic value of programmed cell death-ligand1 (PD-L1) and PD-L2 and to correlate their expression with the degree of infiltration by CD8(+) cells in LAOSCC...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28291636/correlation-between-messenger-rna-expression-and-protein-expression-of-immune-checkpoint-associated-molecules-in-bladder-urothelial-carcinoma-a-retrospective-study
#4
Constance Le Goux, Diane Damotte, Sophie Vacher, Mathilde Sibony, Nicolas Barry Delongchamps, Anne Schnitzler, Benoit Terris, Marc Zerbib, Ivan Bieche, Géraldine Pignot
OBJECTIVES: Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis. METHODS AND MATERIALS: Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients...
March 10, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#5
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28270509/in-situ-and-in-silico-kinetic-analyses-of-the-programmed-cell-death-1-programmed-cell-death-ligands-and-b7-1-interaction-network
#6
Kaitao Li, Xiaoxiao Cheng, Andreas Tilevik, Simon J Davis, Cheng Zhu
Programmed cell death-1 (PD-1) is an inhibitory receptor with an essential role in maintaining peripheral tolerance, and among the most promising immunotherapeutic targets for treating cancer, autoimmunity, and infectious diseases. A complete understanding of the consequences of PD-1 engagement by its ligands, PD-L1 and PD-L2, and of PD-L1 binding to B7-1, requires quantitative analysis of their interactions at the cell surface. We present here the first complete in situ kinetic analysis of the PD-1/PD-1 ligands/B7-1 system...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28265006/characterization-of-the-anti-pd-1-antibody-regn2810-and-its-antitumor-activity-in-human-pd-1-knock-in-mice
#7
Elena Burova, Aynur Hermann, Janelle Waite, Terra Potocky, Venus Lai, Seongwon Hong, Matt Liu, Omaira Allbritton, Amy Woodruff, Qi Wu, Amanda D'Orvilliers, Elena Garnova, Ashique Rafique, William Poueymirou, Joel Martin, Tammy Huang, Dimitris Skokos, Joel Kantrowitz, Jon Popke, Markus Mohrs, Douglas MacDonald, Ella Ioffe, William Olson, Israel Lowy, Andrew Murphy, Gavin Thurston
The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen presenting cells and cancer cells, resulting in suppression of T cell effector function and tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 and PD-L1 restore the cytotoxic function of tumor antigen-specific T cells, yielding durable objective responses in multiple cancers. This report describes the preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4 (S228P) high-affinity anti-PD-1 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2...
March 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28259107/expression-of-programmed-cell-death-ligand-in-cutaneous-squamous-cell-carcinoma-and-treatment-of-locally-advanced-disease-with-pembrolizumab
#8
Mary L Stevenson, Claire Q F Wang, Melody Abikhair, Nazanin Roudiani, Diane Felsen, James G Krueger, Anna C Pavlick, John A Carucci
Importance: Limited therapies are available in patients with inoperable locally advanced cutaneous squamous cell carcinoma (cSCC). Objective: To determine the efficacy of programmed cell death 1 receptor (PD-1) inhibitors in locally advanced cSCC. Design, Setting, and Participants: A single patient with locally advanced cSCC who declined surgery and radiotherapy underwent treatment with pembrolizumab, an anti-PD-1 antibody, at an academic dermatologic surgery section and cancer center...
March 4, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28257800/human-mesenchymal-stem-cell-educated-macrophages-are-a-distinct-high-il-6-producing-subset-that-confer-protection-in-graft-versus-host-disease-and-radiation-injury-models
#9
Myriam N Bouchlaka, Andrea B Moffitt, Jaehyup Kim, John A Kink, Debra D Bloom, Cassandra Love, Sandeep Dave, Peiman Hematti, Christian M Capitini
Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat GVHD have shown mixed results. Macrophages (MØs) are important regulators of immunity and can promote tissue regeneration and remodeling. We have previously shown that MSCs can educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated macrophages or MEMs), however their implications for in vivo models of inflammation have not been studied yet. We now show that in comparison to MØs, MEMs have increased expression of the inhibitory molecules PD-L1, PD-L2, in addition to markers of alternatively activated macrophages: CD206 and CD163...
February 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28256612/the-role-of-indoleamine-2-3-dioxygenase-aryl-hydrocarbon-receptor-pathway-in-the-tlr4-induced-tolerogenic-phenotype-in-human-dcs
#10
Fabián Salazar, Dennis Awuah, Ola H Negm, Farouk Shakib, Amir M Ghaemmaghami
A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28242522/targeting-the-programmed-death-1-pathway-in-lymphoid-neoplasms
#11
REVIEW
Chi Young Ok, Ken H Young
Programmed death-1 (PD-1) is a co-inhibitory molecule and is seen in CD4+ and CD8+ T cells. Upon binding to its ligands, programmed death ligand-1 (PD-L1) and -2 (PD-L2), PD-1 negatively regulates interleukin 2 (IL-2) production and T cell proliferation. Activated effector T-cells, which kill cancer cells, can be affected by PD-1 signaling in some lymphoid neoplasm that express PD-L1 or PD-L2. PD-L1 expression in tumor cells can be induced by extrinsic signal (i.e. interferon gamma) or intrinsic signals, such as genetic aberrations involving 9p24...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#12
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28223102/inflammatory-cytokines-il-17-and-tnf-%C3%AE-up-regulate-pd-l1-expression-in-human-prostate-and-colon-cancer-cells
#13
Xun Wang, Lingyun Yang, Feng Huang, Qiuyang Zhang, Sen Liu, Lin Ma, Zongbing You
Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells...
April 2017: Immunology Letters
https://www.readbyqxmd.com/read/28219001/glut1-as-a-prognostic-factor-for-classical-hodgkin-s-lymphoma-correlation-with-pd-l1-and-pd-l2-expression
#14
Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
BACKGROUND: Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28185924/high-throughput-dynamic-analysis-of-differentially-expressed-genes-in-splenic-dendritic-cells-from-mice-infected-with-schistosoma-japonicum
#15
Lin Chen, Qingzhou Chen, Wei Hou, Li He
Dendritic cells are the initiation and key point of immune response and play a role in immune regulation. So we explored the mechanisms involved in immune regulation of dendritic cells (DCs) against schistosomiasis using mice infected with Schistosoma japonicum. Splenic DCs from normal mice and mice with acute and chronic S. japonicum infection were sorted by flow cytometry. The numbers and functions of differentially expressed genes (DEGs) in DCs were determined by high-throughput analysis. All DEGs with transcription-level fold changes of ≥2 were selected and matched to corresponding genes in databases...
February 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28182273/association-of-time-varying-clearance-of-nivolumab-with-disease-dynamics-and-its-implications-on-exposure-response-analysis
#16
Chao Liu, Jingyu Yu, Hongshan Li, Jiang Liu, Yuan Xu, Pengfei Song, Qi Liu, Hong Zhao, James Xu, Virginia E Maher, Brian P Booth, Geoffrey Kim, Atiqur Rahman, Yaning Wang
Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2. Nivolumab demonstrated efficacy in clinical trials for various types of cancer. A time-varying clearance was identified for nivolumab. We show that the change of clearance over time is associated with the post-treatment effects: clearance decreases when disease status improves. This interaction between post-treatment effects and drug exposure may lead to a biased steep estimate of exposure-response (E-R) relationship for efficacy...
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28169111/expression-pattern-of-immune-checkpoint-associated-molecules-in-radical-nephrectomy-specimens-as-a-prognosticator-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#17
Takuto Hara, Hideaki Miyake, Masato Fujisawa
OBJECTIVE: To analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). METHODS: Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining...
February 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28130401/distinctive-histogenesis-and-immunological-microenvironment-based-on-transcriptional-profiles-of-follicular-dendritic-cell-sarcomas
#18
Maria Antonella Laginestra, Claudio Tripodo, Claudio Agostinelli, Giovanna Motta, Sylvia Hartmann, Claudia Doring, Maura Rossi, Federica Melle, Maria Rosaria Sapienza, Valentina Tabanelli, Alessandro Pileri, Fabio Fuligni, Anna Gazzola, Claudia Mannu, Carlo Alberto Sagramoso, Silvia Lonardi, Luisa Lorenzi, Francesco Bacci, Elena Sabattini, Anita Borges, Ingrid Simonitsch-Klupp, Jose Cabecadas, Elias Campo, Juan Rosai, Martin-Leo Hansmann, Fabio Facchetti, Stefano Aldo Pileri
Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors (MTs) with variable clinical, morphologic and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared to other MTs, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other MTs and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n=1,289) between microdissected FDCs and fibroblasts...
January 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28122135/pd-1-expression-correlates-with-disease-severity-and-il-5-in-chronic-rhinosinusitis-with-nasal-polyps
#19
Inge Kortekaas Krohn, Sonja Bobic, James Dooley, Feng Lan, Nan Zhang, Claus Bachert, Brecht Steelant, Dominique Bullens, Adrian Liston, Jan L Ceuppens, Sven F Seys, Peter W Hellings
BACKGROUND: Programmed cell Death 1 (PD-1) is a negative regulator of T cell responses. Expression of PD-1 and its ligands PD-L1 and PD-L2 in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly studied. METHODS: Expression of PD-1, PD-L1, PD-L2, TGF-β, IL-5 and IL-10 mRNA was measured by RT-PCR on tissue homogenates of patients with CRSwNP (n=21) and healthy controls (n=21) and on primary epithelial cells. Disease severity was scored using the Lund-Mackay scores of maxillo-facial CT scans...
January 25, 2017: Allergy
https://www.readbyqxmd.com/read/28112728/integrated-genomic-and-molecular-characterization-of-cervical-cancer
#20
(no author information available yet)
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib...
March 16, 2017: Nature
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