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pd-l1, lung cancer

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https://www.readbyqxmd.com/read/27913228/pd-l1-immunohistochemistry-assays-for-lung-cancer-results-from-phase-1-of-the-blueprint-pd-l1-ihc-assay-comparison-project
#1
Fred R Hirsch, Abigail McElhinny, Dave Stanforth, James Ranger-Moore, Malinka Jansson, Karina Kulangara, William Richardson, Penny Towne, Debra Hanks, Bharathi Vennapusa, Amita Mistry, Rasika Kalamegham, Steve Averbuch, James Novotny, Eric Rubin, Kenneth Emancipator, Ian McCaffery, J Andrew Williams, Jill Walker, John Longshore, Ming S Tsao, Keith M Kerr
BACKGROUND: The "Blueprint PD-L1 IHC Assay Comparison Project" is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials. METHODS: 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP 142 and SP 263) as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity...
November 29, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27912829/immunotherapy-in-lung-cancer
#2
REVIEW
Lingling Du, Roy S Herbst, Daniel Morgensztern
The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#3
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#4
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#5
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27873079/next-generation-predictive-biomarkers-for-immune-checkpoint-inhibition
#6
Yulian Khagi, Razelle Kurzrock, Sandip Pravin Patel
With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer...
November 21, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27857838/hyponatraemia-secondary-to-nivolumab-induced-primary-adrenal-failure
#7
Harris Trainer, Paul Hulse, Claire E Higham, Peter Trainer, Paul Lorigan
: Checkpoint inhibitors, such as ipilimumab and pembrolizumab, have transformed the prognosis for patients with advanced malignant melanoma and squamous non-small-cell lung cancer, and their use will only expand as experience is gained in a variety of other malignancies, for instance, renal and lymphoma. As the use of checkpoint inhibitors increases, so too will the incidence of their unique side effects, termed immune-related adverse events (irAEs), which can affect dermatological, gastrointestinal, hepatic, endocrine and other systems...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#8
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27846725/-non-small-cell-lung-cancer-from-immunobiology-to-immunotherapy
#9
O Bílek, L Bohovicová, R Demlová, A Poprach, R Lakomý, L Zdražilová-Dubská
BACKGROUND: The treatment of early or locally advanced stages of non-small cell lung cancer (NSCLC) is based on surgical resection or radiotherapy. Metastatic disease is always incurable, treatment is palliative, systemic based on chemotherapy or target therapy. NSCLC is the most common cause of cancer-related death worldwide, and new therapeutic approaches are needed. Based on the emerging data on the role of immune system in shaping of tumor outbreak and outcome, immunotherapy is currently in the center of interest of cancer research and therapy of solid cancers including NSCLC...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27846317/ras-mitogen-activated-protein-kinase-signal-is-required-for-enhanced-pd-l1-expression-in-human-lung-cancers
#10
Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Yataro Daigo
Ectopic programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancers (NSCLCs) is related to immune evasion by cancer, and it is a molecular target of immune checkpoint therapies. Although some altered signals in NSCLCs are responsible for ectopic PD-L1 expression, the precise mechanisms remain obscure. Because we found a higher frequency of EGFR/KRAS mutations in NSCLC cell lines with high PD-L1 expression (p < 0.001), we evaluated the relationships between downstream signals and PD-L1 expression, particularly in three KRAS-mutant adenocarcinoma cell lines...
2016: PloS One
https://www.readbyqxmd.com/read/27843633/scoring-of-pd-l1-expression-intensity-on-pulmonary-adenocarcinomas-and-the-correlations-with-clinicopathological-factors
#11
Tomoyuki Igarashi, Koji Teramoto, Mitsuaki Ishida, Jun Hanaoka, Yataro Daigo
INTRODUCTION: The contribution of programmed cell death ligand-1 (PD-L1) immune checkpoint molecule toward progression of non-small cell lung cancer (NSCLC) has not yet been elucidated, in part, because of lack of a standardised method to evaluate PD-L1 expression. In this study, we developed a novel method for the evaluation of PD-L1 expression on NSCLC cells and examined its correlation with clinicopathological characteristics. METHODS: After immunohistochemical examination of PD-L1 expression for surgically resected pulmonary adenocarcinomas (n=106), based on the findings that PD-L1 are consistently expressed on alveolar macrophages, PD-L1 staining intensity of tumour cells was classified into four levels relative to PD-L1 staining intensity in alveolar macrophages; PD-L1 expression scores (range, 0-300) were semiquantitatively assessed...
2016: ESMO Open
https://www.readbyqxmd.com/read/27834350/quantitative-and-pathologist-read-comparison-of-the-heterogeneity-of-programmed-death-ligand-1-pd-l1-expression-in-non-small-cell-lung-cancer
#12
Jamaal A Rehman, Gang Han, Daniel E Carvajal-Hausdorf, Brad E Wasserman, Vasiliki Pelekanou, Nikita L Mani, Joseph McLaughlin, Kurt A Schalper, David L Rimm
PD-L1 is expressed in a percentage of lung cancer patients and those patients show increased likelihood of response to PD-1 axis therapies. However, the methods and assays for the assessment of PD-L1 using immunohistochemistry are variable and PD-L1 expression appears to be highly heterogeneous. Here, we examine assay heterogeneity parameters toward the goal of determining variability of sampling and the variability due to pathologist-based reading of the immunohistochemistry slide. SP142, a rabbit monoclonal antibody, was used to detect PD-L1 by both chromogenic immunohistochemistry and quantitative immunofluorescence using a laboratory-derived test...
November 11, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27816393/association-of-pd-1-pd-l1-and-ctla-4-gene-expression-and-clinicopathologic-characteristics-in-patients-with-non-small-cell-lung-cancer
#13
Aránzazu Lafuente-Sanchis, Ángel Zúñiga, Miriam Estors, Néstor J Martínez-Hernández, Antonio Cremades, María Cuenca, José M Galbis
INTRODUCTION: Recent studies show a potential benefit of therapies that target programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitory checkpoints in a subgroup of patients with non-small-cell lung cancer (NSCLC), without the clinicopathologic characteristics related to positive responses to these treatments being well determined. The aim of this study was to determine PD-1, PD-L1, and CTLA-4 gene expression at the mRNA level in tumoral tissue from patients with NSCLC and analyze their possible relationship with the clinicopathological characteristics and their potential prognostic role...
October 17, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27816392/assessing-pdl-1-and-pd-1-in-non-small-cell-lung-cancer-a-novel-immunoscore-approach
#14
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee Khanehkenari, Samer Al-Saad, Sigurd M Hald, Sigve Andersen, Elin Richardsen, Nora Ness, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27801735/fading-with-time-of-pd-l1-immunoreactivity-in-non-small-cells-lung-cancer-tissues-a-methodological-study
#15
Francesca Giunchi, Alessio Degiovanni, Niccolò Daddi, Rocco Trisolini, Andrea Dell'Amore, Claudio Agostinelli, Andrea Ardizzoni, Michelangelo Fiorentino
Blockade of inhibitory immune checkpoints is currently arising as a potential immunologic option for tumor therapy. Inhibition of programmed cell death protein 1 and/or its specific ligand programmed death-ligand 1 (PD-L1) was effective in clinical trials in advanced melanoma, non-small cell lung cancer (NSCLC) bladder and kidney cancer. The predictive role of the immunohistochemical (IHC) expression of PD-L1 is highly debated. Different reagents, clones, cutoffs of cell expression and subjective interpretation of PD-L1 immunoreactivity in epithelial cells and lymphocytes are the main issue...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27801734/pd-l1-expression-in-carcinosarcomas-of-the-gynecologic-tract-a-potentially-actionable-biomarker
#16
Andre Pinto, Nicholas Mackrides, Mehrdad Nadji
BACKGROUND: Carcinosarcomas of the gynecologic tract, also known as malignant mixed Müllerian tumors, are aggressive neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. In fact, there are currently no consensus guidelines for the treatment of these neoplasms and the search for targetable biomarkers has not been successful so far. Programmed death-ligand 1 (PD-L1) has emerged as a potential target for therapeutics in a number of malignant tumors, including melanoma, lung, and colorectal cancer...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27799798/high-dose-irradiation-in-combination-with-toll-like-receptor-9-agonist-cpg-oligodeoxynucleotide-7909-downregulates-pd-l1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-non-small-cell-lung-cancer-cells
#17
Xue Chen, Qi Zhang, Youjun Luo, Caixia Gao, Xibing Zhuang, Guoxiong Xu, Tiankui Qiao
OBJECTIVES: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC. MATERIALS AND METHODS: NSCLC H460 cells were exposed to constant high-dose irradiation (6...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27799141/survival-of-lung-adenocarcinoma-patients-predicted-from-expression-of-pd-l1-galectin-9-and-xage1-gaged2a-on-tumor-cells-and-tumor-infiltrating-t-cells
#18
Yoshihiro Ohue, Koji Kurose, Ryohei Nozawa, Midori Isobe, Yumi Nishio, Tomonori Tanaka, Yoshinori Doki, Takashi Hori, Junya Fukuoka, Mikio Oka, Eiichi Nakayama
The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I-IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27793883/immune-blockade-inhibition-in-breast-cancer
#19
REVIEW
Ioannis A Voutsadakis
Besides limited success in treatment of melanoma and renal cell carcinoma, immune treatments of cancer (cancer immunotherapy) had not until recently met the great expectations associated with them over the years. This failure appears now to be reversed with the introduction of checkpoint (immune blockade) inhibitors. Two receptor-ligand checkpoint inhibition pairs, the one based on the inhibition of inhibitory receptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the other based on the inhibition of the programmed death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pair have entered the clinical arena...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27788370/function-of-follicular-helper-t-cell-is-impaired-and-correlates-with-survival-time-in-non-small-cell-lung-cancer
#20
Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Ji Chen, Wendy Miller, Xiao-Feng Chen
Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide. The PD-1/PD-L1 interaction plays important roles in cancer immunology, and expression of PD-L1 has been discovered in NSCLC tumor cells. Since follicular helper T (Tfh) cells have characteristic high PD-1 expression, we therefore investigated the inflammatory status of Tfh in NSCLC. CD4(+)CXCR5(+) T cell population was examined to define Tfh cells. Data showed that frequency of Tfh cells in peripheral blood was significantly lower in NSCLC patients than in healthy controls...
October 24, 2016: International Immunopharmacology
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