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Program death ligand 1/2

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https://www.readbyqxmd.com/read/28345428/induction-of-t-cell-infiltration-and-programmed-death-ligand-2-expression-by-adeno-associated-virus-in-rhesus-macaque-skeletal-muscle-and-modulation-by-prednisone
#1
Megan L Cramer, Guohong Shao, Louise R Rodino-Klapac, Louis G Chicoine, Paul T Martin
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post-AAV delivery compared to AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment...
March 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#2
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#3
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28341875/pd-l1-overexpression-is-partially-regulated-by-egfr-her2-signaling-and-associated-with-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#4
Riki Okita, Ai Maeda, Katsuhiko Shimizu, Yuji Nojima, Shinsuke Saisho, Masao Nakata
Immunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA-IIIA NSCLC...
March 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#5
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
March 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28332100/expression-of-programmed-death-1-and-its-ligands-in-the-liver-of-biliary-atresia
#6
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/28328302/pembrolizumab-for-platinum-and-cetuximab-refractory-head-and-neck-cancer-results-from-a-single-arm-phase-ii-study
#7
Joshua Bauml, Tanguy Y Seiwert, David G Pfister, Francis Worden, Stephen V Liu, Jill Gilbert, Nabil F Saba, Jared Weiss, Lori Wirth, Ammar Sukari, Hyunseok Kang, Michael K Gibson, Erminia Massarelli, Steven Powell, Amy Meister, Xinxin Shu, Jonathan D Cheng, Robert Haddad
Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks...
March 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28319808/identifying-regulatory-posttranslational-modifications-of-pd-l1-a-focus-on-monoubiquitinaton
#8
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
A set of high-affinity, high-specificity posttranslational modification (PTM) enrichment tools was developed to generate an unbiased snapshot of four key PTM profiles (tyrosine phosphorylation, acetylation, ubiquitination, and SUMOylation 2/3) for the clinically important protein programmed cell death ligand 1 (PD-L1). The results showed that epidermal growth factor (EGF) treatment induced tyrosine phosphorylation, acetylation, and ubiquitination of PD-L1. Further characterization of EGF-induced PD-L1 ubiquitination revealed a significant increase in mono- and multiubiquitination of PD-L1 that occurred on glycosylated PD-L1...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28314962/pd-l1-expression-in-pancreatic-ductal-adenocarcinoma-is-a-poor-prognostic-factor-in-patients-with-high-cd8-tumor-infiltrating-lymphocytes-highly-sensitive-detection-using-phosphor-integrated-dot-staining
#9
So Yamaki, Hiroaki Yanagimoto, Koji Tsuta, Hironori Ryota, Masanori Kon
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. METHODS: This study included 42 patients with PDAC who underwent pancreatectomy...
March 18, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28291584/clinical-safety-and-activity-of-pembrolizumab-in-patients-with-malignant-pleural-mesothelioma-keynote-028-preliminary-results-from-a-non-randomised-open-label-phase-1b-trial
#10
Evan W Alley, Juanita Lopez, Armando Santoro, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Emilie van Brummelen
BACKGROUND: Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort. METHODS: Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries...
March 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28278348/a-prospective-multi-institutional-pathologist-based-assessment-of-4-immunohistochemistry-assays-for-pd-l1-expression-in-non-small-cell-lung-cancer
#11
David L Rimm, Gang Han, Janis M Taube, Eunhee S Yi, Julia A Bridge, Douglas B Flieder, Robert Homer, William W West, Hong Wu, Anja C Roden, Junya Fujimoto, Hui Yu, Robert Anders, Ashley Kowalewski, Christopher Rivard, Jamaal Rehman, Cory Batenchuk, Virginia Burns, Fred R Hirsch, Ignacio I Wistuba
Importance: Four assays registered with the US Food and Drug Administration (FDA) detect programmed cell death ligand 1 (PD-L1) to enrich for patient response to anti-programmed cell death 1 and anti-PD-L1 therapies. The tests use 4 separate PD-L1 antibodies on 2 separate staining platforms and have their own scoring systems, which raises questions about their similarity and the potential interchangeability of the tests. Objective: To compare the performance of 4 PD-L1 platforms, including 2 FDA-cleared assays, 1 test for investigational use only, and 1 laboratory-developed test...
March 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28275222/pd-1-pd-l1-protein-expression-in-non-small-cell-lung-cancer-and-their-relationship-with-tumor-infiltrating-lymphocytes
#12
Yayi He, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafał Dziadziuszko, Hui Yu, Caicun Zhou, Fred R Hirsch
BACKGROUND Immunotherapy targeting the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint has shown the good outcomes in non-small cell lung cancer (NSCLC). We investigated PD-1 and PD-L1 protein expression and their correlation with tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC. MATERIAL AND METHODS The expression of PD-1 (NAT105, Cell Marque) and PD-L1 (28-8, Dako) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC). PD-1 (NAT105, Cell Marque) and PD-L1 (22C3, Dako) protein expression was evaluated by IHC, and TIL percentage was scored, in 139 surgically resected specimens from patients with NSCLC...
March 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28275115/safety-and-tolerability-of-pd-1-pd-l1-inhibitors-compared-with-chemotherapy-in-patients-with-advanced-cancer-a-meta-analysis
#13
Tomohiro F Nishijima, Shlomit S Shachar, Kirsten A Nyrop, Hyman B Muss
BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016...
March 8, 2017: Oncologist
https://www.readbyqxmd.com/read/28267244/a-multicenter-phase-ii-study-of-nivolumab-in-japanese-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma
#14
Dai Maruyama, Kiyohiko Hatake, Tomohiro Kinoshita, Noriko Fukuhara, Ilseung Choi, Masafumi Taniwaki, Kiyoshi Ando, Yasuhito Terui, Yusuke Higuchi, Yasushi Onishi, Yasunobu Abe, Tsutomu Kobayashi, Yukari Shirasugi, Kensei Tobinai
Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR)...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28267224/prognostic-value-of-programmed-death-ligand-1-expression-in-patients-with-stage-iii-colorectal-cancer
#15
Shigehiro Koganemaru, Naoko Inoshita, Yuji Miura, Yu Miyama, Yudai Fukui, Yukinori Ozaki, Kenji Tomizawa, Yutaka Hanaoka, Shigeo Toda, Koichi Suyama, Yuko Tanabe, Jin Moriyama, Takeshi Fujii, Shuichiro Matoba, Hiroya Kuroyanagi, Toshimi Takano
The Programmed death-1/ Programmed death-ligand 1 (PD-L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD-L1 expression on tumor cells (TCs) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of this study was to evaluate the relationship between PD-L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28263231/appendix-derived-pseudomyxoma-peritonei-pmp-molecular-profiling-toward-treatment-of-a-rare-malignancy
#16
Elizabeth M Gleeson, Rebecca Feldman, Beth L Mapow, Lynn T Mackovick, Kristine M Ward, William F Morano, Rene R Rubin, Wilbur B Bowne
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization)...
March 3, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28259530/association-between-pd-l1-expression-and-driven-gene-status-in-nsclc-a-meta-analysis
#17
D Li, X Zhu, H Wang, N Li
PURPOSE: We explored the potential clinical association between programmed death-ligand 1 (PD-L1) expression and driven gene status in non-small cell lung cancer (NSCLC). METHODS: We systemically searched through October 2015. Odd ratios (ORs) with 95% CIs were calculated to examine the association of PD-L1 expression with driven gene status. A random- or fixed-effects model was used. RESULTS: Nine studies were identified. KRAS-mutant tumors were more likely to be PD-L1 positive than KRAS-wild type tumors (51% vs 36%; OR 1...
February 21, 2017: European Journal of Surgical Oncology
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
#18
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/28257959/the-immune-microenvironment-genome-wide-copy-number-aberrations-and-survival-in-mesothelioma
#19
Bibhusal Thapa, Adriana Salcedo, Xihui Lin, Marzena Walkiewicz, Carmel Murone, Malaka Ameratunga, Khashyar Asadi, Siddhartha Deb, Stephen Arthur Barnett, Simon Knight, Paul Mitchell, D Neil Watkins, Paul C Boutros, Thomas John
INTRODUCTION: Results of recent clinical studies of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) have dampened initial enthusiasm. However, the immune environment and targets of these treatments such as program cell death protein 1 (PD-1) and its ligand PD-L1 have not been well characterised in MPM. Using a large cohort of patients, we investigated PD-L1 expression, immune infiltrates and genome-wide copy number status and correlated them to clinicopathological features...
February 28, 2017: Journal of Thoracic Oncology
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
#20
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
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