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https://www.readbyqxmd.com/read/29792909/dermatofibrosarcoma-protuberans-a-retrospective-study-of-clinicopathological-features-and-related-akt-mtor-stat3-erk-cyclin-d1-and-pd-l1-expression
#1
Sunyoung Park, Soyun Cho, Minji Kim, Ji Ung Park, Eui Cheol Jeong, Euno Choi, Jeong Hwan Park, Cheol Lee, Mee Soo Chang
BACKGROUND: Little is known regarding oncoproteins other than PDGFβ in dermatofibrosarcoma protuberance (DFSP). Moreover, the risk factors for worse prognosis are controversial. OBJECTIVE: We sought to determine the clinicopathological features and key factors for adverse outcome in DFSP including the implication of Akt/mTOR, STAT3, ERK, cyclinD1, and PD-L1 expression. METHODS: Clinicopathological and immunohistochemical analyses were performed for 44 DFSPs having wide local excision along with 92 dermatofibromas as controls...
May 21, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#2
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#3
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789013/prognostic-significance-of-pd-l1-expression-and-cd8-t-cell-infiltration-in-pulmonary-neuroendocrine-tumors
#4
Haiyue Wang, Zhongwu Li, Bin Dong, Wei Sun, Xin Yang, Ruping Liu, Lixin Zhou, Xiaozheng Huang, Ling Jia, Dongmei Lin
BACKGROUND: Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors. METHODS: In total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study...
May 22, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29787423/autoimmune-granulomatous-inflammation-of-lacrimal-glands-and-axonal-neuritis-following-treatment-with-ipilimumab-and-radiation-therapy
#5
Ecaterina Ileana Dumbrava, Veronica Smith, Rasha Alfattal, Adel K El-Naggar, Marta Penas-Prado, Apostolia M Tsimberidou
Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response...
May 21, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29787422/activity-of-pembrolizumab-in-recurrent-cervical-cancer-case-series-and-review-of-published-data
#6
Marlene Kranawetter, Sebastian Röhrich, Leonhard Müllauer, Helena Obermair, Alexander Reinthaller, Christoph Grimm, Alina Sturdza, Wolfgang J Köstler, Stephan Polterauer
OBJECTIVES: Recent data support the use of pembrolizumab in cervical cancer. The aim of this study was to investigate pembrolizumab in heavily pretreated patients with recurrent cervical cancer. METHODS: Data from consecutive patients treated with pembrolizumab at a single academic institution were assessed. Programmed cell death ligand 1 (PD-L1) status and microsatellite instability were assessed from tumor samples. Irrespective of PD-L1 expression status, pembrolizumab was administered at fixed dose of 200 mg intravenously every 3 weeks...
May 22, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29786078/targeting-the-upstream-transcriptional-activator-of-pd-l1-as-an-alternative-strategy-in-melanoma-therapy
#7
Bo Zhu, Liming Tang, Shuyang Chen, Chengqian Yin, Shiguang Peng, Xin Li, Tongzheng Liu, Wei Liu, Changpeng Han, Lukasz Stawski, Zhi-Xiang Xu, Guangbiao Zhou, Xiang Chen, Xiumei Gao, Colin R Goding, Nan Xu, Rutao Cui, Peng Cao
Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2)...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29785577/atezolizumab-a-review-in-previously-treated-advanced-non-small-cell-lung-cancer
#8
REVIEW
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29784449/a-radiosensitivity-gene-signature-and-pd-l1-predict-the-clinical-outcomes-of-patients-with-lower-grade-glioma-in-tcga
#9
Bum-Sup Jang, In Ah Kim
PURPOSE: Identifying predictive factors for the clinical outcome of patients with lower grade gliomas following radiotherapy could help optimize patient treatments. Here, we investigate the predictive efficacy of both a previously identified "31-gene signature" and programmed death ligand-1 (PD-L1) expression. MATERIAL AND METHODS: We identified 511 patients with lower grade glioma (Grade 2 and 3) in The Cancer Genome Atlas dataset and divided them into two clusters: radiosensitive (RS) and radioresistant (RR)...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#10
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29779430/intratumoral-immune-cells-expressing-pd-1-pd-l1-and-their-prognostic-implications-in-cancer-a-meta-analysis
#11
Younghoon Kim, Xianyu Wen, Nam Yun Cho, Gyeong Hoon Kang
BACKGROUND: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. METHODS: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival...
May 1, 2018: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29779068/new-insights-into-the-inflamed-tumor-immune-microenvironment-of-gastric-cancer-with-lymphoid-stroma-from-morphology-and-digital-analysis-to-gene-expression
#12
Irene Gullo, Patrícia Oliveira, Maria Athelogou, Gilza Gonçalves, Marta L Pinto, Joana Carvalho, Ana Valente, Hugo Pinheiro, Sara Andrade, Gabriela M Almeida, Ralf Huss, Kakoli Das, Patrick Tan, José C Machado, Carla Oliveira, Fátima Carneiro
BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations...
May 19, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#13
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#14
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29776424/impaired-cd8-t-cell-antiviral-immunity-following-acute-spinal-cord-injury
#15
Diana M Norden, John R Bethea, Jiu Jiang
BACKGROUND: Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI. METHODS: One week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus...
May 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#16
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#17
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#18
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29774031/il-10-producing-b-cells-ability-to-induce-regulatory-t-cells-is-maintained-in-rheumatoid-arthritis
#19
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773717/stk11-lkb1-mutations-and-pd-1-inhibitor-resistance-in-kras-mutant-lung-adenocarcinoma
#20
Ferdinandos Skoulidis, Michael E Goldberg, Danielle M Greenawalt, Matthew D Hellmann, Mark M Awad, Justin F Gainor, Alexa B Schrock, Ryan J Hartmaier, Sally E Trabucco, Laurie Gay, Siraj M Ali, Julia A Elvin, Gaurav Singal, Jeffrey S Ross, David Fabrizio, Peter M Szabo, Han Chang, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph Szustakowski, Patrik Vitazka, Robin Edwards, Jose A Bufill, Neelesh Sharma, Sai-Hong I Ou, Nir Peled, David R Spigel, Hira Rizvi, Elizabeth Jimenez Aguilar, Brett W Carter, Jeremy Erasmus, Darragh F Halpenny, Andrew J Plodkowski, Niamh M Long, Mizuki Nishino, Warren L Denning, Ana Galan-Cobo, Haifa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez-Canales, Pamela A Villalobos, Edwin R Parra, Neda Kalhor, Lynette M Sholl, Jennifer L Sauter, Achim A Jungbluth, Mari Mino-Kenudson, Roxana Azimi, Yasir Y Elamin, Jianjun Zhang, Giulia C Leonardi, Fei Jiang, Kwok-Kin Wong, J Jack Lee, Vassiliki A Papadimitrakopoulou, Ignacio I Wistuba, Vincent A Miller, Garrett M Frampton, Jedd D Wolchok, Alice T Shaw, Pasi A Jänne, Philip J Stephens, Charles M Rudin, William J Geese, Lee A Albacker, John V Heymach
KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) co-mutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P<0.001) in the SU2C cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase 3 trial (0% vs 57...
May 17, 2018: Cancer Discovery
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