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https://www.readbyqxmd.com/read/27926587/anti-programmed-cell-death-protein-1-tolerance-and-efficacy-after-ipilimumab-immunotherapy-observational-study-of-39-patients
#1
Reyhan Amode, Barouyr Baroudjian, Anita Kowal, Majdi Jebali, Clara Allayous, Martine Bagot, Nika Madjlessi, Jennifer Roux, Manuelle Viguier, Nicole Basset Seguin, Raphaël Porcher, Cécile Pagès, Céleste Lebbé
In patients with ipilimumab (IPI)-refractory melanoma, the anti-programmed cell death proteins 1 (PD1s) nivolumab (NIV) and pembrolizumab (PEM) are considered to be a new standard of treatment. Few data are available on anti-PD1 safety in patients who develop IPI-related severe adverse events (AEs) (grade≥3). The aim of this study was to compare the anti-PD1 safety and efficacy in patients with previous severe toxicity to IPI versus in those showing moderate and no previous IPI-related AEs. This single institution-based observational study included all patients treated with anti-PD1 (PEM or NIV) and previously treated with IPI for unresectable stage III or IV melanoma...
December 6, 2016: Melanoma Research
https://www.readbyqxmd.com/read/27914594/association-of-pdcd1-polymorphism-to-systemic-lupus-erythematosus-and-rheumatoid-arthritis-susceptibility
#2
Luisa Matos do Canto, Ticiana Della Justina Farias, Mayara Delagnelo Medeiros, Cíntia Callegari Coêlho, Aline Fernanda Rodrigues Sereia, Lia Kubelka Fernandes de Carlos Back, Filipe Martins de Mello, Adriana Fontes Zimmermann, Ivânio Alves Pereira, Ilíada Rainha de Souza
OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0...
November 2016: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#3
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911126/anti-pd1-treatment-in-metastatic-uveal-melanoma-in-the-netherlands
#4
M K van der Kooij, A Joosse, F M Speetjens, G A P Hospers, C Bisschop, J W B de Groot, R Koornstra, C U Blank, E Kapiteijn
No abstract text is available yet for this article.
December 2, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27900319/spleen-dependent-immune-protection-elicited-by-cpg-adjuvanted-reticulocyte-derived-exosomes-from-malaria-infection-is-associated-with-changes-in-t-cell-subsets-distribution
#5
Lorena Martín-Jaular, Armando de Menezes-Neto, Marta Monguió-Tortajada, Aleix Elizalde-Torrent, Míriam Díaz-Varela, Carmen Fernández-Becerra, Francesc E Borras, Maria Montoya, Hernando A Del Portillo
Reticulocyte-derived exosomes (rex) are 30-100 nm membrane vesicles of endocytic origin released during the maturation of reticulocytes to erythrocytes upon fusion of multivesicular bodies with the plasma membrane. Combination of CpG-ODN with rex obtained from BALB/c mice infected with the reticulocyte-prone non-lethal P. yoelii 17X malaria strain (rexPy), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon rexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with rexPy+CpG...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#6
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/27892773/real-world-data-on-nivolumab-treatment-of-non-small-cell-lung-cancer
#7
O T Brustugun, M Sprauten, Å Helland
BACKGROUND: Checkpoint inhibitors have proven effectiveness in clinical trials for non-small cell lung cancer (NSCLC) patients, but if this is congruent with routine patient care is discussed. We present real-world experience with the PD1-inhibitor nivolumab in NSCLC. PATIENTS AND METHODS: Patients with NSCLC were considered eligible for nivolumab treatment after one or more lines of chemotherapy, and when in reasonable performance status (PS) [Eastern Cooperative Oncology Group (ECOG) < 3]...
November 28, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27891189/variations-in-dna-methylation-of-interferon-gamma-and-programmed-death-1-in-allograft-rejection-after-kidney-transplantation
#8
Karin Boer, L Elly A de Wit, Fleur S Peters, Dennis A Hesselink, Leo J Hofland, Michiel G H Betjes, Caspar W N Looman, Carla C Baan
BACKGROUND: The role of DNA methylation in the regulation of the anti-donor-directed immune response after organ transplantation is unknown. Here, we studied the methylation of two mediators of the immune response: the pro-inflammatory cytokine interferon γ (IFNγ) and the inhibitory receptor programmed death 1 (PD1) in naïve and memory CD8+ T cell subsets in kidney transplant recipients receiving immunosuppressive medication. Both recipients experiencing an episode of acute allograft rejection (rejectors) as well as recipients without rejection (non-rejectors) were included...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27885401/-cutaneous-side-effects-of-targeted-cancer-drugs
#9
REVIEW
J Below, B Homey, P A Gerber
In the past decades many new drugs were approved for the treatment of cancer and have been established as essential parts of various therapeutic regimens. In particular targeted therapies and immune checkpoint inhibitors that aim at specific carcinogenic signaling pathways or modulate the tumor-immune response have revolutionized cancer therapy. Despite their targeted actions, these drugs may lead to diverse adverse reactions. In particular, cutaneous toxicities represent a serious threat to patients' quality of life and may lead to dose reduction or therapy cessation...
November 24, 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/27879972/responses-of-metastatic-basal-cell-and-cutaneous-squamous-cell-carcinomas-to-anti-pd1-monoclonal-antibody-regn2810
#10
Gerald S Falchook, Rom Leidner, Elizabeth Stankevich, Brian Piening, Carlo Bifulco, Israel Lowy, Matthew G Fury
BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly mutated tumors are more likely to express immunogenic tumor neoantigens that attract effector T cells, which can be unleashed by blockade of the PD-1 immune checkpoint...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27873300/local-checkpoint-inhibition-of-ctla-4-as-a-monotherapy-or-in-combination-with-anti-pd1-prevents-the-growth-of-murine-bladder-cancer
#11
Luuk van Hooren, Linda C Sandin, Igor Moskalev, Peter Ellmark, Anna Dimberg, Peter Black, Thomas H Tötterman, Sara M Mangsbo
Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic MB49 bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown subcutaneously, peritumoral injection of anti-CTLA-4 treatment was equally effective as intravenous or subcutaneous (non-tumor bearing flank) administration...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27872087/tim-3-expression-on-tumor-infiltrating-pd-1-cd8-t-cells-correlates-with-poor-clinical-outcome-in-renal-cell-carcinoma
#12
Clémence Granier, Charles Dariane, Pierre Combe, Virginie Verkarre, Saik Urien, Cecile Badoual, Hélène Roussel, Marion Mandavit, Patrice Ravel, Mathilde Sibony, Lucie Biard, Camelia Radulescu, Emeline Vinatier, Nadine Benhamouda, Michael Peyromaure, Stephane Oudard, Arnaud Méjean, Marc Olivier Timsit, Alain Gey, Eric Tartour
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27868139/clinical-genetic-and-innate-immunity-characteristics-of-melanoma-in-organ-transplant-recipients
#13
Anabelle Brocard, Anne-Chantal Knol, Céline Bossard, Marc G Denis, Gaëlle Quéreux, Mélanie Saint-Jean, Lucie Peuvrel, Amir Khammari, Gilles Blancho, Jacques Dantal, Brigitte Dréno
The aims of this study were to determine the clinical and histological characteristics of melanoma in transplant recipients, the mutation profile (BRAF, NRAS and c-KIT genes), and the immune tolerance of the tumour microenvironment by immunohistochemical study of the expression of IDO, PD1, PD-L1, CD8 and FoxP3. The study population comprised patients who had undergone a renal transplant in Nantes University Hospital who developed post-transplantation melanoma. Twenty cases of melanoma out of 4,663 transplant recipients were studied...
November 10, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27867002/trametinib-plus-4-methylumbelliferone-exhibits-antitumor-effects-by-erk-blockade-and-cd44-downregulation-and-affects-pd1-and-pd-l1-in-malignant-pleural-mesothelioma
#14
Hiroyuki Cho, Seiji Matsumoto, Yoshiko Fujita, Ayumi Kuroda, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Ikuko Torii, Takashi Nakano, Primo N Lara, David R Gandara, Hiroshi Date, Seiki Hasegawa
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy in which the mitogen-activated protein kinase (MAPK) pathway plays a critical role in the regulation of tumorigenesis. Hyaluronan (HA) is a major component of the extracellular matrix, and elevated HA levels, with a concurrent increase in malignant properties, are associated with MPM. METHODS: We evaluated the effects of trametinib, a MAPK kinase enzyme (MEK) inhibitor, and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in combination on MPM cells in vitro and in vivo...
November 17, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27864215/atrophic-exocrine-pancreatic-insufficiency-associated-with-anti-pd1-therapy
#15
G Long, A Hoadley, N Sandanayake
No abstract text is available yet for this article.
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27855687/diagnostic-accuracy-of-methacholine-challenge-tests-assessing-airway-hyperreactivity-in-asthmatic-patients-a-multifunctional-approach
#16
Richard Kraemer, Hans-Jürgen Smith, Thomas Sigrist, Gabi Giger, Roland Keller, Martin Frey
BACKGROUND: There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose-response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic accuracy of several lung function parameters quantitating AHR by dose-response characteristics. METHODS: Changes in effective specific airway conductance (sGeff) as estimate of the degree of bronchial obstruction were compared with concomitantly measured forced expiratory volume in 1 s (FEV1) and forced expiratory flows at 50% forced vital capacity (FEF50)...
November 17, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27853858/production-process-reproducibility-and-product-quality-consistency-of-transient-gene-expression-in-hek293-cells-with-anti-pd1-antibody-as-the-model-protein
#17
Kai Ding, Lei Han, Huifang Zong, Junsheng Chen, Baohong Zhang, Jianwei Zhu
Demonstration of reproducibility and consistency of process and product quality is one of the most crucial issues in using transient gene expression (TGE) technology for biopharmaceutical development. In this study, we challenged the production consistency of TGE by expressing nine batches of recombinant IgG antibody in human embryonic kidney 293 cells to evaluate reproducibility including viable cell density, viability, apoptotic status, and antibody yield in cell culture supernatant. Product quality including isoelectric point, binding affinity, secondary structure, and thermal stability was assessed as well...
November 16, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27834344/inhibiting-macrophage-pi3k%C3%AE-to-enhance-immunotherapy
#18
Wei Zheng, Jeffrey W Pollard
A recent paper published in Nature reports that the immunosuppressive activity of tumor-associated macrophages is regulated via PI3Kγ signaling. Small-molecule inhibitors targeting PI3Kγ stimulate T cell activity against tumor alone and add additional effects for clinically proven PD1 immunotherapy.
December 2016: Cell Research
https://www.readbyqxmd.com/read/27832664/acute-interstitial-nephritis-related-to-immune-checkpoint-inhibitors
#19
Julie Belliere, Nicolas Meyer, Julien Mazieres, Sylvie Ollier, Serge Boulinguez, Audrey Delas, David Ribes, Stanislas Faguer
BACKGROUND: Immune checkpoint inhibitors (anti-PD1 or anti-CTLA-4) are increasingly used in various cancers. Immune checkpoint inhibitors (ICI)-related renal disorders are poorly described (9 cases) and were only related to Ipilimumab. METHODS: Retrospective collection of clinical charts of all the patients admitted for renal disorders following ICI in the University Hospital of Toulouse (France). RESULTS: We report on adverse renal events that occurred in three patients treated with anti-PD1 (nivolumab or pembrolizumab) or anti-CTLA-4 (ipilimumab)...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#20
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
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