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Program death ligand 1/2

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https://www.readbyqxmd.com/read/29469949/safety-profile-of-avelumab-in-patients-with-advanced-solid-tumors-a-pooled-analysis-of-data-from-the-phase-1-javelin-solid-tumor-and-phase-2-javelin-merkel-200-clinical-trials
#1
Karen Kelly, Jeffrey R Infante, Matthew H Taylor, Manish R Patel, Deborah J Wong, Nicholas Iannotti, Janice M Mehnert, Anja H Loos, Helga Koch, Isabell Speit, James L Gulley
BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks...
February 22, 2018: Cancer
https://www.readbyqxmd.com/read/29468855/major-clinical-research-advances-in-gynecologic-cancer-in-2017
#2
REVIEW
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29467301/oncogenic-jak2-v617f-causes-pd-l1-expression-mediating-immune-escape-in-myeloproliferative-neoplasms
#3
Alessandro Prestipino, Alica J Emhardt, Konrad Aumann, David O'Sullivan, Sivahari P Gorantla, Sandra Duquesne, Wolfgang Melchinger, Lukas Braun, Slavica Vuckovic, Melanie Boerries, Hauke Busch, Sebastian Halbach, Sandra Pennisi, Teresa Poggio, Petya Apostolova, Pia Veratti, Michael Hettich, Gabriele Niedermann, Mark Bartholomä, Khalid Shoumariyeh, Jonas S Jutzi, Julius Wehrle, Christine Dierks, Heiko Becker, Annette Schmitt-Graeff, Marie Follo, Dietmar Pfeifer, Jan Rohr, Sebastian Fuchs, Stephan Ehl, Frederike A Hartl, Susana Minguet, Cornelius Miething, Florian H Heidel, Nicolaus Kröger, Ioanna Triviai, Tilman Brummer, Jürgen Finke, Anna L Illert, Eliana Ruggiero, Chiara Bonini, Justus Duyster, Heike L Pahl, Steven W Lane, Geoffrey R Hill, Bruce R Blazar, Nikolas von Bubnoff, Erika L Pearce, Robert Zeiser
Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F -mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F -mutant cells...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29462123/pembrolizumab-for-the-treatment-of-advanced-salivary-gland-carcinoma-findings-of-the-phase-1b-keynote-028-study
#4
Roger B Cohen, Jean-Pierre Delord, Toshihiko Doi, Sarina A Piha-Paul, Stephen V Liu, Jill Gilbert, Alain P Algazi, Silvia Damian, Ruey-Long Hong, Christophe Le Tourneau, Daphne Day, Andrea Varga, Elena Elez, John Wallmark, Sanatan Saraf, Pradeep Thanigaimani, Jonathan Cheng, Bhumsuk Keam
OBJECTIVES: Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored. MATERIALS AND METHODS: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay)...
February 21, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29458244/clinical-and-molecular-characteristics-of-pulmonary-sarcomatoid-carcinoma
#5
Jae Kyeom Sim, Sang Mi Chung, Jong Hyun Choi, Jee Youn Oh, Seung Heon Lee, Je Hyeong Kim, Kyung Hoon Min, Gyu Young Hur, Jae Jeong Shim, Kyung Ho Kang, Bong Kyung Shin, Ju Han Lee, Sung Yong Lee
Background/Aims: Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated non-small cell lung cancer (NSCLC) that contains components of spindle or giant cells. Owing to its low prevalence, there are insufficient data regarding its clinical features, therapeutic strategies and prognosis. Methods: The medical records of 26 patients diagnosed with PSC from January 2009 to June 2015 were reviewed and analyzed for clinicopathological characteristics, treatment modality, and outcomes...
February 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29455872/-pd-l1-expression-and-pd-1-pd-l1-inhibitors-in-breast-cancer
#6
REVIEW
Audrey Monneur, Anthony Gonçalves, François Bertucci
The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing)...
February 15, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29455638/the-clinicopathological-and-prognostic-significance-of-programmed-cell-death-ligand-1-pd-l1-expression-in-patients-with-non-medullary-thyroid-cancer-a-systematic-review-and-meta-analysis
#7
Marra Aghajani, Susannah Graham, Charles McCafferty, Christina Abdel Shaheed, Tara Roberts, Paul DeSouza, Tao Yang, Navin Niles
BACKGROUND: Evidence has shown that PD-L1 overexpression is associated with poor prognosis and resistance to immune therapies in several human cancers. However, data on the prognostic significance of PD-L1 expression in thyroid cancer is limited and remains controversial. In this systematic review and meta-analysis, we aimed to comprehensively evaluate the clinicopathological significance and prognostic value of PD-L1 expression in non-medullary thyroid cancers. SUMMARY: Electronic databases, including Medline/PubMed, EMBASE and the Cochrane Library, were searched up until July 5th, 2017...
February 17, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29450544/hla-class-i-antigen-expression-in-conjunctival-melanoma-is-not-associated-with-pd-l1-pd-1-status
#8
Jinfeng Cao, Niels J Brouwer, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd G van Duinen, Nadine E de Waard, Bruce R Ksander, Arend Mulder, Frans H J Claas, Mirjam H M Heemskerk, Martine J Jager
Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#9
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435162/prognostic-value-of-pd-l1-expression-in-patients-with-primary-solid-tumors
#10
Xiao Xiang, Peng-Cheng Yu, Di Long, Xiao-Li Liao, Sen Zhang, Xue-Mei You, Jian-Hong Zhong, Le-Qun Li
Programmed death-ligand 1 (PD-L1) is thought to play a critical role in immune escape by cancer, but whether PD-L1 expression can influence prognosis of patients with solid tumors is controversial. Therefore, we meta-analyzed available data on whether PD-L1 expression correlates with overall survival (OS) in such patients. PubMed, EMBASE and other databases were systematically searched for cohort or case-control studies examining the possible correlation between PD-L1 expression and OS of patients with solid tumors...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29433902/safety-and-efficacy-of-pd-1-pd-l1-inhibitors-in-treatment-naive-and-chemotherapy-refractory-patients-with-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#11
Monica Khunger, Prantesh Jain, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors...
January 10, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29431467/correlation-between-programmed-death-receptor-1-expression-in-tumor-infiltrating-lymphocytes-and-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinoma
#12
Paloma Del C Monroig-Bosque, Brandon Driver, Joel A Morales-Rosado, Michael Deavers, David Tacha, Eric Bernicker, Philip T Cagle, Ross A Miller
CONTEXT: - The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non-small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease. OBJECTIVE: - To investigate the correlation of PD-1 and PD-L1 in non-small cell lung carcinoma tumor samples, with emphasis on stage I disease...
February 12, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29427150/programmed-death-ligand-1-expression-and-tumor-infiltrating-lymphocytes-in-neurofibromatosis-type-1-and-2-associated-tumors
#13
Shiyang Wang, Benjamin Liechty, Seema Patel, Jeffrey S Weber, Travis J Hollmann, Matija Snuderl, Matthias A Karajannis
Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD-L1 expression on tumor cells, as well as the presence of tumor infiltrating lymphocytes (TILs). It is currently unknown whether tumors associated with neurofibromatosis types 1 and 2 (NF1 and NF2) express PD-L1. We performed immunohistochemistry for PD-L1 (clones SP142 and E1L3N), CD3, CD20, CD8, and CD68 in NF1-related tumors (ten dermal and six plexiform neurofibromas) and NF2-related tumors (ten meningiomas and ten schwannomas) using archival formalin-fixed paraffin-embedded tissues...
February 9, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29426340/pd-l1-diagnostic-tests-a-systematic-literature-review-of-scoring-algorithms-and-test-validation-metrics
#14
REVIEW
Margarita Udall, Maria Rizzo, Juliet Kenny, Jim Doherty, SueAnn Dahm, Paul Robbins, Eric Faulkner
BACKGROUND: The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer types express PD-L1 and evade immune recognition via the PD-1/PD-L1 interaction. Precision therapies targeting the PD-1/PD-L1 pathway have the potential to improve response and thereby offer a novel treatment avenue to some patients with cancer. However, this new therapeutic approach requires reliable methods for identifying patients whose cancers are particularly likely to respond...
February 9, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29423515/atezolizumab-mpdl3280a-monotherapy-for-patients-with-metastatic-urothelial-cancer-long-term-outcomes-from-a-phase-1-study
#15
Daniel P Petrylak, Thomas Powles, Joaquim Bellmunt, Fadi Braiteh, Yohann Loriot, Rafael Morales-Barrera, Howard A Burris, Joseph W Kim, Beiying Ding, Constanze Kaiser, Marcella Fassò, Carol O'Hear, Nicholas J Vogelzang
Importance: Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective: To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants: Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study...
February 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29419471/increased-levels-of-soluble-programmed-death-ligand-1-associate-with-malignancy-in-patients-with-dermatomyositis
#16
He Chen, Qinglin Peng, Hanbo Yang, Liguo Yin, Jingli Shi, Yamei Zhang, Guochun Wang
OBJECTIVE: To investigate the levels of soluble programmed death ligand 1 (sPD-L1) and evaluate its association with malignancy in patients with dermatomyositis (DM). METHODS: Levels of sPD-L1 were measured in serum from 88 DM patients without malignancies (sDM), 40 with cancer-related DM (CRDM), and 30 healthy controls (HC) using ELISA. The CRDM subjects were divided into new-onset cancers (nCRDM) and stable cancers (sCRDM). Receiver-operating characteristic (ROC) curve analysis was performed to determine the cutoff sPD-L1 value that distinguished patients with nCRDM from those who were sDM...
February 1, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29409471/pd-l1-expression-in-malignant-salivary-gland-tumors
#17
Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
BACKGROUND: Programmed death-1 ligand-1 (PD-L1) an important cancer biomarker that can suppress the immune system and its high expression is often reported to be related with increased tumor aggressiveness in some cancers. Here, we examined and evaluated PD-L1 expression in patients with malignant salivary gland tumor. Moreover, the relationship between PD-L1 immunolocalization and clinical pathological features, as well as the prognosis of malignant salivary gland tumors was investigated...
February 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29405663/cytologic-histologic-correlation-of-programmed-death-ligand-1-immunohistochemistry-in-lung-carcinomas
#18
Eleanor Russell-Goldman, Sasha Kravets, Suzanne E Dahlberg, Lynette M Sholl, Marina Vivero
BACKGROUND: Programmed cell death protein 1 inhibitors increasingly are being used to treat patients with advanced lung carcinomas. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) is used to select patients for programmed cell death protein 1 inhibition, but few studies have evaluated PD-L1 IHC in cytology specimens. The objective of the current study was to compare PD-L1 IHC in cytology cell blocks and matched surgical specimens...
February 5, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29403496/recent-advances-in-targeting-cd8-t-cell-immunity-for-more-effective-cancer-immunotherapy
#19
REVIEW
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29402391/ifn-%C3%AE-and-tumor-gangliosides-implications-for-the-tumor-microenvironment
#20
Barbara Dillinger, Sarah Ahmadi-Erber, Manuel Lau, Markus A Hoelzl, Friedrich Erhart, Birgit Juergens, Dietmar Fuchs, Andreas Heitger, Stephan Ladisch, Alexander M Dohnal
Gangliosides shed by tumors into their microenvironment (TME) are immunoinhibitory. Interferon-γ (IFN-γ) may boost antitumor immune responses. Thus we wondered whether IFN-γ would counteract tumor ganglioside-mediated immune suppression. To test this hypothesis, we exposed human monocyte-derived LPS-activated dendritic cells (DC) to IFN-γ and to a highly purified ganglioside, GD1a. DC ganglioside exposure decreased TLR-dependent p38 signaling, explaining the previously observed ganglioside-induced down-modulation of pro-inflammatory surface markers and cytokines...
February 2, 2018: Cellular Immunology
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