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https://www.readbyqxmd.com/read/28919999/first-report-of-clinical-responses-to-immunotherapy-in-3-relapsing-cases-of-chordoma-after-failure-of-standard-therapies
#1
Denis Migliorini, Nicolas Mach, Diego Aguiar, Rémi Vernet, Basile Nicolas Landis, Minerva Becker, Thomas McKee, Valérie Dutoit, Pierre-Yves Dietrich
Chordoma is a rare tumor of notochordal origin, currently principally treated by surgery and/or irradiation. Here, we describe the clinical outcome of 3 consecutive patients with metastatic and locally advanced chordoma, treated with different immunotherapeutic approaches. All patients presented fast growing tumors and failure of standard therapies. One was treated with a tumor-based vaccine, the 2 others with anti-PD1 antibodies, all with impressive clinical and radiological responses. We therefore propose that chordoma is an immunogenic tumor and thus that translational and clinical research is necessary to develop rationally designed immunotherapy approaches...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#2
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28881692/cabazitaxel-in-recurrent-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-phase-ii-unicancer-trial-orl03
#3
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878768/natural-igm-and-tlr-agonists-switch-murine-splenic-pan-b-to-regulatory-cells-that-suppress-ischemia-induced-innate-inflammation-via-regulating-nkt-1-cells
#4
Peter I Lobo, Kailo H Schlegel, Amandeep Bajwa, Liping Huang, Mark D Okusa
Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878208/hsp90-inhibition-enhances-cancer-immunotherapy-by-upregulating-interferon-response-genes
#5
Rina M Mbofung, Jodi A McKenzie, Shruti Malu, Min Zhang, Weiyi Peng, Chengwen Liu, Isere Kuiatse, Trang Tieu, Leila Williams, Seram Devi, Emily Ashkin, Chunyu Xu, Lu Huang, Minying Zhang, Amjad H Talukder, Satyendra C Tripathi, Hiep Khong, Nikunj Satani, Florian L Muller, Jason Roszik, Timothy Heffernan, James P Allison, Gregory Lizee, Sam M Hanash, David Proia, Rodabe Amaria, R Eric Davis, Patrick Hwu
T-cell-based immunotherapies are promising treatments for cancer patients. Although durable responses can be achieved in some patients, many patients fail to respond to these therapies, underscoring the need for improvement with combination therapies. From a screen of 850 bioactive compounds, we identify HSP90 inhibitors as candidates for combination with immunotherapy. We show that inhibition of HSP90 with ganetespib enhances T-cell-mediated killing of patient-derived human melanoma cells by their autologous T cells in vitro and potentiates responses to anti-CTLA4 and anti-PD1 therapy in vivo...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28877189/programmed-cell-death-1-pd-1-is-dysregulated-in-t-cells-from-children-with-new-onset-type-1-diabetes
#6
Hector M Granados, Andrew Draghi, Naomi Tsurutani, Kyle Wright, Marina L Fernandez, Francisco A Sylvester, Anthony T Vella
BACKGROUND: Programmed death cell 1 (PD-1) is an inhibitor of T cell activation and is also functionally linked to glycolysis. We hypothesized that PD-1 expression is defective in activated T cells from children with type 1 diabetes (T1D), resulting in abnormal T cell glucose metabolism. METHODS: In this pilot study, we enrolled children with new onset T1D within 2 weeks of diagnosis (T1D), unaffected siblings of T1D (SIBS), unaffected, unrelated children (CTRL), children with new onset, and untreated Crohn disease (CD)...
2017: PloS One
https://www.readbyqxmd.com/read/28873125/neurological-complications-associated-with-anti-programmed-death-1-pd-1-antibodies
#7
Justin C Kao, Bing Liao, Svetomir N Markovic, Christopher J Klein, Elie Naddaf, Nathan P Staff, Teerin Liewluck, Julie E Hammack, Paola Sandroni, Heidi Finnes, Michelle L Mauermann
Importance: Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. Objective: To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016...
September 5, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28870260/programmed-cell-death-ligand-1-cut-point-is-associated-with-reduced-disease-specific-survival-in-resected-pancreatic-ductal-adenocarcinoma
#8
Basile Tessier-Cloutier, Steve E Kalloger, Mohammad Al-Kandari, Katy Milne, Dongxia Gao, Brad H Nelson, Daniel J Renouf, Brandon S Sheffield, David F Schaeffer
BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In this study, we explore the staining characteristics, prevalence, and clinico-molecular correlates of PD-L1 overexpression in pancreatic ductal adenocarcinoma (PDAC). METHODS: A tissue microarray (TMA) was constructed from cases of resected PDAC...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28869918/circulating-cd4-pd-1-and-cd8-pd-1-t-cells-are-profoundly-decreased-at-the-onset-of-fulminant-type-1-diabetes-and-are-restored-by-treatment-contrasting-with-cd4-cd25-foxp3-regulatory-t-cells
#9
Toshie Iijima, Kanako Kato, Teruo Jojima, Takanori Tomotsune, Maiko Fukushima, Kunihiro Suzuki, Yoshimasa Aso
Programed cell death protein-1 (PD-1) is an inhibitory receptor expressed by T cells that downregulates the activation and proliferation of these cells to maintain peripheral self-tolerance. Recent studies reported some cases of new-onset type 1 diabetes (T1D) under anti-PD1 or PDL-1 antibodies. We demonstrated that circulating both CD4+PD-1+ and CD8+PD-1+ T cells were profoundly reduced at the onset of fulminant T1D and were restored by treatment in two patients with fulminant T1D.
July 31, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28861116/enabling-a-genetically-informed-approach-to-cancer-medicine-evaluation-of-the-impact-of-comprehensive-tumor-sequencing
#10
Elizabeth J Davis, Douglas B Johnson
"The role of next-generation sequencing to determine appropriateness of anti-PD1/PD-L1 therapy needs further investigation, but has shown promise in predicting response and survival in melanoma and urothelial carcinoma."
May 2017: Personalized Medicine
https://www.readbyqxmd.com/read/28838649/brachytherapy-attains-abscopal-effects-when-combined-with-immunostimulatory-monoclonal-antibodies
#11
María E Rodriguez-Ruiz, Inmaculada Rodriguez, Benigno Barbes, Lina Mayorga, Alfonso Rodriguez Sanchez-Paulete, Mariano Ponz-Sarvise, José Luis Pérez-Gracia, Ignacio Melero
PURPOSE/OBJECTIVES: Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal effects of radiotherapy instigated by brachytherapy techniques...
August 21, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28836129/enlighting-the-shadow-for-advanced-hepatocellular-carcinoma-immunotherapy-with-immune-checkpoint-inhibitors
#12
REVIEW
Berksoy Sahin
Hepatocellular carcinoma has still been one of the cancer with increasing incidence and highest mortality rate in the world. Although many new promising developments have been defined in hepatocarcinogenesis, with a short survival the treatment of patients with advanced hepatocellular carcinoma is an emerging issue. On the recent decade, only one anti-angiogenic agent sorafenib improved overall survival with costing a hardly manageable toxicity. Novel immunotherapeutic agents, especially immune checkpoint inhibitors are on the edge of more effective but less toxic treatments for these patients...
August 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28818609/multicenter-comparison-of-22c3-pharmdx-agilent-and-sp263-ventana-assays-to-test-pd-l1-expression-for-nsclc-patients-to-be-treated-with-immune-checkpoint-inhibitors
#13
Antonio Marchetti, Massimo Barberis, Renato Franco, Graziano De Luca, Maria Vittoria Pace, Stefania Staibano, Marco Volante, Fiamma Buttitta, Elena Guerini-Rocco, Luisella Righi, Tommaso D'antuono, Giorgio V Scagliotti, Carmine Pinto, Gaetano De Rosa, Mauro Papotti
INTRODUCTION: Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of non-small cell lung cancer patients in association with a companion diagnostic assay, the anti-programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) 22C3 PharmDx (Agilent) using the Dako Autostainer. However, the Dako platform is not present in each pathology department and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#14
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28783540/survival-of-melanoma-patients-treated-with-targeted-therapy-and-immunotherapy-after-systematic-upfront-control-of-brain-metastases-by-radiosurgery
#15
C Gaudy-Marqueste, A S Dussouil, R Carron, L Troin, N Malissen, A Loundou, S Monestier, S Mallet, M A Richard, J M Régis, J J Grob
BACKGROUND: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. PATIENTS AND METHODS: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice...
August 4, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28770269/the-pd-1-pd-l1-inhibitory-pathway-is-altered-in-primary-glomerulonephritides
#16
Ewelina Grywalska, Iwona Smarz-Widelska, Ewelina Krasowska-Zajac, Izabela Korona-Glowniak, Karolina Zaluska-Patel, Michal Mielnik, Martyna Podgajna, Anna Malm, Jacek Rolinski, Wojciech Zaluska
The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time...
August 2, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28753231/pd-1-inhibitor-associated-lichenoid-inflammation-with-incidental-suprabasilar-acantholysis-or-vesiculation-report-of-4-cases
#17
Shaun Chou, Cathy Zhao, Shelley Ji Eun Hwang, Pablo Fernandez-Penas
BACKGROUND: Immune checkpoint agents targeting programmed cell death-1 protein (PD1) or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) receptors are increasingly utilized in treatment of advanced malignancies. However, these immunotherapies are commonly associated with idiosyncratic cutaneous adverse reactions. Thus, recognition and awareness of these reactions are necessary. METHODS: We reviewed the skin biopsies of all patients on anti-PD1 therapy with or without ipilimumab who developed lichenoid inflammation and included those with microscopic suprabasal or intraepidermal clefts...
July 28, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28739711/adrenal-insufficiency-related-to-anti-programmed-death-1-therapy
#18
Ryo Ariyasu, Atsushi Horiike, Takahiro Yoshizawa, Yosuke Dotsu, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Shingo Nishikawa, Satoru Kitazono, Noriko Yanagitani, Makoto Nishio
BACKGROUND/AIM: Adrenal insufficiency is one of the adverse events (AEs) associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can lead to serious conditions. It is necessary to elucidate detailed clinical features of these AEs. PATIENTS AND METHODS: Patients treated with anti-PD-1 monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at our hospital from January 2013 to December 2016 were identified. The patients' clinical characteristics and laboratory and radiologic findings were collected...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#19
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#20
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
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