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PD1 cancer

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https://www.readbyqxmd.com/read/28429196/expression-of-programmed-cell-death-protein-1-by-tumor-infiltrating-lymphocytes-and-tumor-cells-is-associated-with-advanced-tumor-stage-in-patients-with-esophageal-adenocarcinoma
#1
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Matthias Paireder, Ivan Kristo, Dmitry Kazakov, Michal Michal, Antonio Cozzio, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Emmanuella Guenova, Sebastian F Schoppmann
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28420659/very-low-expression-of-pd-l1-in-medullary-thyroid-carcinoma
#2
Massimo Bongiovanni, Caterina Rebecchini, Chiara Saglietti, Jean-Luc Bulliard, Laura Marino, Laurence De Leval, Gerasimos P Sykiotis
Monoclonal antibodies that inhibit the interaction between PD1 and PD-L1 are approved for clinical use in several cancer types, and they are also in clinical trials for additional indications, including thyroid carcinomas. A few papers have reported on PD-L1 expression in thyroid carcinomas, including a recent large study by Ahn et al. in Endocrine-Related Cancer using tissue microarrays on differentiated and anaplastic thyroid carcinoma. However, the expression of PD-L1 in medullary thyroid carcinoma (MTC) has not been reported so far, even though ongoing clinical studies aim to test the effectiveness of checkpoint inhibitors in this rare histotype as well...
April 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#3
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407370/inflammation-triggered-cancer-immunotherapy-by-programmed-delivery-of-cpg-and-anti-pd1-antibody
#4
Chao Wang, Wujin Sun, Grace Wright, Andrew Z Wang, Zhen Gu
No abstract text is available yet for this article.
April 2017: Advanced Materials
https://www.readbyqxmd.com/read/28404956/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#5
Jerome Fayette, Joel Guigay, Christophe Le Tourneau, Marian Degardin, Frederic Peyrade, Eve-Marie Neidhardt, Marie-Paule Sablin, Caroline Even, Florence Orlandini, Béata Juzyna, Carine Bellera
Treatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy.This multicenter phase II trial included progressive patients with an ECOG ≤2...
March 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400429/genomic-analysis-of-thymic-epithelial-tumors-identifies-novel-subtypes-associated-with-distinct-clinical-features
#6
Hyun-Sung Lee, Hee-Jin Jang, Rohan Shah, David Yoon, Masatsugu Hamaji, Ori Wald, Ju-Seog Lee, David J Sugarbaker, Bryan M Burt
PURPOSE To reconcile the heterogeneity of thymic epithelial tumors (TETs) and gain deeper understanding of the molecular determinants of TETs, we set out to establish a clinically relevant molecular classification system for these tumors. <p>EXPERIMENTAL DESIGN Molecular subgrouping of TETs was performed in 120 patients from The Cancer Genome Atlas using a multidimensional approach incorporating analyses of DNA mutations, mRNA expression, and somatic copy number alterations (SCNA), and validated in two independent cohorts...
April 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28389693/the-advantages-and-challenges-of-using-fdg-pet-ct-for-response-assessment-in-melanoma-in-the-era-of-targeted-agents-and-immunotherapy
#7
REVIEW
Annie N M Wong, Grant A McArthur, Michael S Hofman, Rodney J Hicks
The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably...
April 7, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28383817/cd70-and-pdl1-in-anaplastic-thyroid-cancer-ndash-promising-targets-for-immunotherapy
#8
Karen Zwaenepoel, Julie Jacobs, Astrid De Meulenaere, Karen Silence, Evelien Smits, Vasiliki Siozopoulou, Esther Hauben, Christian Rolfo, Sylvie Rottey, Patrick Pauwels
AIMS: Over the last years, immune checkpoint inhibition has proven to be effective in several solid malignancies. The aim of this study was to identify novel targets for immunotherapy in anaplastic thyroid cancer by analysis of the expression of tumor antigens for which therapeutic agents are available. METHOD AND RESULTS: By immunohistochemistry we observed tumoral expression of CD70 in 49% of cases. Expression of its receptor, CD27 was mainly present in lymphocytes surrounding and infiltrating the tumor and only rarely observed in tumor cells...
April 6, 2017: Histopathology
https://www.readbyqxmd.com/read/28367063/understanding-the-role-of-pd-l1-pd1-pathway-blockade-and-autophagy-in-cancer-therapy
#9
REVIEW
Marianela Robainas, Rafael Otano, Stephen Bueno, Sihem Ait-Oudhia
Autophagy is a vital, physiological catabolic process for cell survival by which cells clear damaged organelles and recycle nutrients when homeostasis is maintained. Cancer is a complex disease with uncontrolled growth of cancer cells. Recent studies have suggested the role of autophagy in cancer. A complex relationship exists between autophagy and cancer, since autophagy can contribute to the survival or the destruction of malignant cells depending on the stage of tumor development. In this review, we describe in detail the mechanism underlying autophagy in cancer cells and the intricate involvement of the programmed cell death-1 (PD1) receptor with its ligand (PD-L1)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28351930/hyper-progressors-after-immunotherapy-analysis-of-genomic-alterations-associated-with-accelerated-growth-rate
#10
Shumei Kato, Aaron Michael Goodman, Vighnesh Walavalkar, Donald A Barkauskas, Andrew Sharabi, Razelle Kurzrock
PURPOSE: Checkpoint inhibitors demonstrate salutary anti-cancer effects including long-term remissions. PD-L1 expression/amplification, high mutational burden and mismatch repair-deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyper-progressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared to pre-therapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic markers associated with "hyper-progression" after immunotherapy...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28349740/immunotherapy-for-gastric-cancers-emerging-role-and-future-perspectives
#11
Marta Bonotto, Silvio Ken Garattini, Debora Basile, Elena Ongaro, Valentina Fanotto, Monica Cattaneo, Francesco Cortiula, Donatella Iacono, Giovanni Gerardo Cardellino, Nicoletta Pella, Gianpiero Fasola, Lorenzo Antonuzzo, Nicola Silvestris, Giuseppe Aprile
The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers...
March 28, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#12
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#13
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#14
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28325631/new-concepts-of-personalized-therapy-in-salivary-gland-carcinomas
#15
REVIEW
Gunter Keller, Diana Steinmann, Alexander Quaas, Viktor Grünwald, Stefan Janssen, Kais Hussein
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options...
March 18, 2017: Oral Oncology
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#16
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
May 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#17
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 30, 2017: Nature
https://www.readbyqxmd.com/read/28276698/the-role-of-checkpoint-inhibitors-immunotherapy-in-advanced-non-small-cell-lung-cancer-in-the-elderly
#18
Assunta Sgambato, Francesca Casaluce, Cesare Gridelli
Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC. Several molecules targeting cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 receptor/programmed death ligand-1 (PD1/PD-L1) pathways are under evaluation in NSCLC and three of them are currently approved: nivolumab and atezolizumab for advanced NSCLC after prior chemotherapy and pembrolizumab for advanced NSCLC expressing PD-L1 ≥ 1% after at least one prior chemotherapy regimen and > 50% as a first-line response...
February 20, 2017: Expert Opinion on Biological Therapy
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
#19
REVIEW
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...
April 2017: Oncologist
https://www.readbyqxmd.com/read/28271729/egfr-tki-combination-with-immunotherapy-in-non-small-cell-lung-cancer
#20
REVIEW
Myung-Ju Ahn, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has significantly improved clinical outcomes compared with chemotherapy in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR gene mutation. Areas covered: Almost all patients treated with EGFR TKIs eventually develop acquired resistance. It has been reported that activation of the oncogenic EGFR pathway enhances susceptibility of the lung tumors to PD-1 blockade in mouse model, suggesting combination of PD1 blockade with EGFR TKIs may be a promising therapeutic strategy...
April 2017: Expert Opinion on Drug Safety
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