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https://www.readbyqxmd.com/read/28646772/prevalence-of-immune-related-systemic-adverse-events-in%C3%A2-patients-treated-with-anti-programmed-cell-death-1-anti-programmed-cell-death-ligand-1-agents-a-single-centre-pharmacovigilance-database-analysis
#1
Sébastien Le Burel, Stéphane Champiat, Christine Mateus, Aurélien Marabelle, Jean-Marie Michot, Caroline Robert, Rakiba Belkhir, Jean-Charles Soria, Salim Laghouati, Anne-Laure Voisin, Olivier Fain, Arsène Mékinian, Laetitia Coutte, Tali-Anne Szwebel, Laetitia Dunogeant, Bertrand Lioger, Cécile Luxembourger, Xavier Mariette, Olivier Lambotte
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28645564/immunotherapy-holds-the-key-to-cancer-treatment-and-prevention-in-constitutional-mismatch-repair-deficiency-cmmrd-syndrome
#2
Harm Westdorp, Sigrid Kolders, Nicoline Hoogerbrugge, I Jolanda M de Vries, Marjolijn C J Jongmans, Gerty Schreibelt
Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations in MMR genes. This syndrome is characterized by the development of childhood cancer. Patients with CMMRD are at extremely high risk of developing multiple cancers including hematological, brain and intestinal tumors...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28645491/systematic-review-of-immune-checkpoint-inhibition-in-urological-cancers
#3
REVIEW
Maud Rijnders, Ronald de Wit, Joost L Boormans, Martijn P J Lolkema, Astrid A M van der Veldt
CONTEXT: In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs). OBJECTIVE: To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. EVIDENCE ACQUISITION: Relevant databases, including Medline, Embase, and the Cochrane Library, were searched up to March 16, 2017...
June 20, 2017: European Urology
https://www.readbyqxmd.com/read/28644837/real-world-first-line-treatment-and-overall-survival-in-non-small-cell-lung-cancer-without-known-egfr-mutations-or-alk-rearrangements-in-us-community-oncology-setting
#4
Amy P Abernethy, Ashwini Arunachalam, Thomas Burke, Caroline McKay, Xiting Cao, Rachael Sorg, David P Carbone
PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015)...
2017: PloS One
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#5
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28644433/ctla-4-mediated-posttranslational-modifications-direct-cytotoxic-t-lymphocyte-differentiation
#6
Holger Lingel, Josef Wissing, Aditya Arra, Denny Schanze, Stefan Lienenklaus, Frank Klawonn, Mandy Pierau, Martin Zenker, Lothar Jänsch, Monika C Brunner-Weinzierl
The blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8(+) T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#7
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#8
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28642817/cerebral-vasculitis-mimicking-intracranial-metastatic-progression-of-lung-cancer-during-pd-1-blockade
#9
Heinz Läubli, Jürgen Hench, Michal Stanczak, Ingmar Heijnen, Alexandros Papachristofilou, Stephan Frank, Alfred Zippelius, Frank Stenner-Liewen
BACKGROUND: Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management. CASE PRESENTATION: Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28641702/-prospect-and-current-situation-of-immune-checkpoint-inhibitors-%C3%A2-in-first-line-treatment-in-advanced-non-small-cell-lung-cancer-patients
#10
Haiyang Wang, Xiaoqing Yu, Yun Fan
With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#11
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#12
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28639951/metabolic-abnormalities-and-oxidative-stress-in-lupus
#13
Yaima L Lightfoot, Luz P Blanco, Mariana J Kaplan
PURPOSE OF REVIEW: Upon antigen exposure, immune cells rely on cell-specific metabolic pathways to mount an efficient immune response. In autoimmunity, failure in critical metabolic checkpoints may lead to immune cell hyperactivation and tissue damage. Oxidative stress in autoimmune patients can also contribute to immune dysregulation and injury to the host. Recent insights into the immune cell metabolism signatures, specifically associated with systemic lupus erythematosus (SLE) and the consequences of heightened oxidative stress in patients, are discussed herein...
July 20, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28639883/cancer-immunotherapy-breakthrough-or-deja-vu-all-over-again
#14
Stewart Sell
From the application of Coley's toxin in the early 1900s to the present clinical trials using immune checkpoint regulatory inhibitors, the history of cancer immunotherapy has consisted of extremely high levels of enthusiasm after anecdotal case reports of enormous success, followed by decreasing levels of enthusiasm as the results of controlled clinical trials are available. In this review, this pattern will be documented for the various immunotherapeutic approaches over the years. The sole exception being vaccination against cancer causing viruses, which have already prevented thousands of cancers...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#15
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28638461/current-status-of-immune-checkpoint-inhibitors-in-gastrointestinal-cancers
#16
REVIEW
Bum Jun Kim, Hyun Joo Jang, Hyeong Su Kim, Jung Han Kim
The expansion of our understanding of tumor immunity and the recent success of new cancer immunotherapy has reignited the hope that we can treat cancer effectively with immunotherapeutic approaches. Immune checkpoint inhibitors have shown significant efficacy in the treatment of some solid and hematologic malignancies. Encouraged by recent success in some other types of malignancies, many clinical trials are ongoing to evaluate the efficacy of immune checkpoint inhibitors in gastrointestinal (GI) malignancies...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#17
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636222/recent-progress-in-immunotherapy-for-urological-cancer
#18
REVIEW
Wataru Obara, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata
Cancer immunotherapy for urological tumors had made progress for several decades, but recent advances in immunotherapy, as therapeutic vaccines or immune checkpoint inhibitors, have drastically changed the present treatment strategy. Recently, nivolumab and atezolizumab have been approved by the Food and Drug Administration for treatment of urological cancers. Additional immune checkpoint inhibitors and vaccines are being tested in clinical trials. Despite advances in these therapeutic modalities, benefits are limited to a subset of patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#19
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#20
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
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