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immunotherapy biomarker

Michelle M Kim, Yoshie Umemura, Denise Leung
Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with few advances in treatment over the last several decades. Much excitement surrounded the initial approval for bevacizumab for recurrent GBM, given the marked radiographic responses and improvement in progression-free survival observed in early studies. However, phase III studies have failed to demonstrate an overall survival advantage with the use of this agent. An overview of the mechanism of action and activity of bevacizumab in adult gliomas, a timeline of pivotal clinical trials, data on its impact on quality of life and imaging, and its role in managing the sequelae of treatment provide evidence for its current use...
July 2018: Cancer Journal
Yujiao Zhou, Feifei Liu, Chengmin Li, Guo Shi, Xiaolei Xu, Xue Luo, Yuanling Zhang, Jingjie Fu, Aizhong Zeng, Limin Chen
Dendritic cells (DCs) harboring tumor-associated antigen are supposed to be a potential immunotherapy for hepatocellular carcinoma (HCC). Aspartate- β -hydroxylase (AAH), an overexpressed tumor-associated cell surface protein, is considered as a promising biomarker and therapeutic target for HCC. In this study, we constructed adenovirus vector encoding AAH gene by gateway recombinant cloning technology and preliminarily explored the antitumor effects of DC vaccines harboring AAH. Firstly, the total AAH mRNA was extracted from human HCC tissues; the cDNA was amplified by RT-PCR, verified, and sequenced after TA cloning...
2018: Journal of Immunology Research
Cun-Yi Zou, Ge-Fei Guan, Chen Zhu, Tian-Qi Liu, Qing Guo, Wen Cheng, An-Hua Wu
AIMS: Immune checkpoint blockade has made breakthroughs in immunotherapy for glioma. However, current immunotherapy has therapeutic benefits only in a subset of patients and accompanied by immune-related side effects. SLAMF8 is a costimulatory molecule that affects the activation of macrophages in inflammation. The study of SLAMF8 may provide new information for immunological research and treatment of glioma. METHODS: CGGA and TCGA cohorts of 946 patients with RNA sequencing data and full clinical information were analyzed using R language and GraphPad Prism 7...
August 13, 2018: CNS Neuroscience & Therapeutics
Ankur Chakravarthy, Andrew Furness, Kroopa Joshi, Ehsan Ghorani, Kirsty Ford, Matthew J Ward, Emma V King, Matt Lechner, Teresa Marafioti, Sergio A Quezada, Gareth J Thomas, Andrew Feber, Tim R Fenton
The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: 'immune hot' and 'immune cold', which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity and oncogenic driver events...
August 13, 2018: Nature Communications
Jiajia Zhang, Shafat Quadri, Christopher L Wolfgang, Lei Zheng
Biomarkers refer to a plethora of biological characteristics that can be quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and predict a response to treatment. The identification of objective biomarkers is among the most crucial steps in the realization of individualized cancer care. Several tumor biomarkers for gastrointestinal malignancies have been applied in the clinical setting to help differentiate between cancer and other conditions, facilitate patient selection for targeted therapies, and to monitor treatment response and recurrence...
August 13, 2018: Biomedicines
Mirco Friedrich, Lukas Bunse, Wolfgang Wick, Michael Platten
PURPOSE OF REVIEW: The present review introduces recent progress in eliciting the role of mutant isocitrate dehydrogenase (IDH) in gliomas, especially regarding its mode of action as a modulator of antitumor immune response, and provides rationales for targeting mutant IDH in glioma immunotherapy. Both the development of small molecule inhibitors repressing the enzymatic activity of mutant IDH and novel, mechanism-led combination immunotherapies are discussed. RECENT FINDINGS: Since the discovery of highly frequent IDH mutations in low-grade gliomas and nonsolid malignancies, its tumor cell-intrinsic effects have been intensively investigated...
August 9, 2018: Current Opinion in Oncology
Stefan Rutkowski, Piergiorgio Modena, Daniel Williamson, Kornelius Kerl, Karsten Nysom, Barry Pizer, Ute Bartels, Stephanie Puget, François Doz, Antony Michalski, Katja von Hoff, Mathilde Chevignard, Shivaram Avula, Matthew J Murray, Stefan Schönberger, Thomas Czech, Antoinette Y N Schouten-van Meeteren, Uwe Kordes, Christof M Kramm, Dannis G van Vuurden, Esther Hulleman, Geert O Janssens, Guirish A Solanki, Marie-Luise C van Veelen, Ulrich Thomale, Martin U Schuhmann, Chris Jones, Felice Giangaspero, Dominique Figarella-Branger, Torsten Pietsch, Steve C Clifford, Stefan M Pfister, Stefaan W Van Gool
Paediatric CNS tumours are the most common cause of childhood cancer-related morbidity and mortality, and improvements in their diagnosis and treatment are needed. New genetic and epigenetic information about paediatric CNS tumours is transforming the field dramatically. For most paediatric CNS tumour entities, subgroups with distinct biological characteristics have been identified, and these characteristics are increasingly used to facilitate accurate diagnoses and therapeutic recommendations. Future treatments will be further tailored to specific molecular subtypes of disease, specific tumour predisposition syndromes, and other biological criteria...
August 2018: Lancet Oncology
Siqing Fu, Yudong Wang, Khandan Keyomarsi, Funda Meric-Bernstein
Wee1 kinase controls the G2-M checkpoint. Wee1 inhibition by AZD1775 allows cells with a deregulated G1 checkpoint to progress, resulting in catastrophe and apoptosis. The challenges ahead are in the establishment of the optimum dosing schedule either alone or in combination, and the identification of patients with specific biomarker profiles who benefit most. Areas covered: This article provides an overview of AZD1775, based on English peer-reviewed articles on MEDLINE. The authors highlight the data from the published preclinical and clinical studies...
August 13, 2018: Expert Opinion on Investigational Drugs
Michäel Duruisseaux, Anna Martínez-Cardús, Maria E Calleja-Cervantes, Sebastian Moran, Manuel Castro de Moura, Veronica Davalos, David Piñeyro, Montse Sanchez-Cespedes, Nicolas Girard, Marie Brevet, Etienne Giroux-Leprieur, Coraline Dumenil, Monica Pradotto, Paolo Bironzo, Enrica Capelletto, Silvia Novello, Alexis Cortot, Marie-Christine Copin, Niki Karachaliou, Maria Gonzalez-Cao, Sergio Peralta, Luis M Montuenga, Ignacio Gil-Bazo, Iosune Baraibar, Maria D Lozano, Mar Varela, Jose C Ruffinelli, Ramon Palmero, Ernest Nadal, Teresa Moran, Lidia Perez, Immaculada Ramos, Qingyang Xiao, Agustin F Fernandez, Mario F Fraga, Marta Gut, Ivo Gut, Cristina Teixidó, Noelia Vilariño, Aleix Prat, Noemi Reguart, Amparo Benito, Pilar Garrido, Isabel Barragan, Jean-François Emile, Rafael Rosell, Elisabeth Brambilla, Manel Esteller
BACKGROUND: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. METHODS: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease...
August 9, 2018: Lancet Respiratory Medicine
Guy Ben-Betzalel, Erez N Baruch, Ben Boursi, Yael Steinberg-Silman, Nethanel Asher, Ronnie Shapira-Frommer, Jacob Schachter, Gal Markel
BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are among the cornerstones of metastatic melanoma therapy demonstrating excellent response rates with duration of 7-12 m. Long-term benefit from these agents was reported in patients with normal lactate dehydrogenase (LDH) and less than three disease sites. However, a treatment-dependent marker for long-term efficacy is lacking. Data suggest that immune-related adverse events (irAEs) are associated with clinical benefit in patients treated with immunotherapy and that response to BRAF/MEK therapy may have an underlying immune mechanism...
August 7, 2018: European Journal of Cancer
Ana Luísa Coelho, Mónica Patrícia Gomes, Raquel Jorge Catarino, Christian Rolfo, Rui Manuel Medeiros, António Manuel Araújo
Background: Lung cancer is the most incident and lethal form of cancer, with late diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting immune checkpoints improve survival, but positive results encompass only 30%-40% of the patients, possibly due to alternative pathways to immunosuppression, including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF-1) is implicated in TAM differentiation and recruitment to tumours and in tumour angiogenesis, through a special setting of Tie-2-expressing macrophages, which respond to angiopoietin-2 (Ang-2)...
2018: ESMO Open
Jingjing Duan, Yu Wang, Shunchang Jiao
A dynamic and mutualistic interaction between tumor cells and tumor microenvironment (TME) promotes the progression and metastasis of solid tumors. Cancer immunotherapy is becoming a major treatment paradigm for a variety of cancers. Although immunotherapy, especially the use of immune checkpoint inhibitors, has achieved clinical success, only a minority of patients exhibits durable responses. Clinical studies directed at identifying appropriate biomarkers and immune profiles that can be used to predict immunotherapy responses are presently being conducted...
August 7, 2018: Cancer Medicine
David R Gandara, Sarah M Paul, Marcin Kowanetz, Erica Schleifman, Wei Zou, Yan Li, Achim Rittmeyer, Louis Fehrenbacher, Geoff Otto, Christine Malboeuf, Daniel S Lieber, Doron Lipson, Jacob Silterra, Lukas Amler, Todd Riehl, Craig A Cummings, Priti S Hegde, Alan Sandler, Marcus Ballinger, David Fabrizio, Tony Mok, David S Shames
Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer (NSCLC). However, obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging. Thus, an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy...
August 6, 2018: Nature Medicine
Arezoo Rasti, Mitra Mehrazma, Zahra Madjd, Maryam Abolhasani, Leili Saeednejad Zanjani, Mojgan Asgari
Many renal cancer patients experience disease recurrence after combined treatments or immunotherapy due to permanence of cancer stem cells (CSCs). This study was conducted to evaluate the expression patterns and clinical significance of octamer-binding transcription factor 4 (OCT4) and NANOG as the key stem cell factors in renal cell carcinoma (RCC). A total of 186 RCC tissues were immunostained on a tissue microarray (TMA) for the putative CSC markers OCT4 and NANOG. Subsequently, the correlation among the expression of these markers, the clinicopathological variables and survival outcomes were determined...
August 6, 2018: Scientific Reports
Laura Ridolfi, Francesco de Rosa, Laura Fiammenghi, Massimiliano Petrini, Anna Maria Granato, Valentina Ancarani, Elena Pancisi, Valentina Soldati, Serena Cassan, Jenny Bulgarelli, Angela Riccobon, Giorgia Gentili, Oriana Nanni, Massimo Framarini, Francesca Tauceri, Massimo Guidoboni
INTRODUCTION: Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases...
August 5, 2018: BMJ Open
Mark T Mackay, Maja Steinlin
This review will discuss important developments in childhood arterial ischemic stroke over the past decade, focusing on improved understanding of the causes, consequences, and targets for intervention. Risk factors for childhood arterial ischemic stroke are different to adults. Infections, particularly herpes group viruses, are important precipitants for stroke. Non-atherosclerotic arteriopathies are the most common cause of childhood arterial ischemic stroke and an important predictor of recurrent events. Recent advances include the identification of serum biomarkers for inflammation and endothelial injury, and imaging biomarkers to monitor for vascular progression...
August 6, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
Weijing Cai, Dapeng Zhou, Weibo Wu, Wen Ling Tan, Jiaqian Wang, Caicun Zhou, Yanyan Lou
BACKGROUND: Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody. RESULTS: In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules...
August 3, 2018: BMC Genomics
Daniela Femia, Natalie Prinzi, Andrea Anichini, Roberta Mortarini, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Andrea Maurichi, Ilaria Mattavelli, Massimo Milione, Nice Bedini, Ambra Corti, Maria Di Bartolomeo, Filippo de Braud, Sara Pusceddu
Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches...
August 2, 2018: Targeted Oncology
Shigehisa Kitano, Takayuki Nakayama, Makiko Yamashita
Immune checkpoint inhibitors have now become a standard therapy for malignant melanoma. However, as immunotherapies are effective in only a limited number of patients, biomarker development remains one of the most important clinical challenges. Biomarkers predicting clinical benefit facilitate appropriate selection of individualized treatments for patients and maximize clinical benefits. Many biomarkers derived from tumors and peripheral blood components have recently been reported, mainly in retrospective settings...
2018: Frontiers in Oncology
Bracha Shraibman, Eilon Barnea, Dganit Melamed Kadosh, Yael Haimovich, Gleb Slobodin, Itzhak Rosner, Carlos López-Larrea, Norbert Hilf, Sabrina Kuttruff, Colette Song, Cedrik Britten, John Castle, Sebastian Kreiter, Katrin Frenzel, Marcos Tatagiba, Ghazaleh Tabatabai, Pierre-Yves Dietrich, Valérie Dutoit, Wolfgang Wick, Michael Platten, Frank Winkler, Andreas Von Deimling, Judith Kroep, Juan Sahuquillo, Francisco Martinez-Ricarte, Jordi Rodon, Ulrik Lassen, Christian Ottensmeier, Sjoerd H van der Burg, Per Thor Straten, Hans Skovgaard Poulsen, Berta Ponsati, Hideho Okada, Hans Georg Rammensee, Ugur Sahin, Harpreet Singh, Arie Admon
Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples...
August 2, 2018: Molecular & Cellular Proteomics: MCP
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