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Tumour immunology

Daniel M Altmann
The field of cancer immunology stepped into the limelight this year when James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation. Among many exciting advances contributing to the coming of age of tumour immunology as a viable clinical specialty has been the ability to progress from the initial elucidation of tumour antigens, such as the melanoma antigen, MAGE-1, to high-throughput sequencing facilitating identification of T cell epitopes from diverse tumour neoantigens...
November 2018: Immunology
V Brie, M Faure, J Garon, I Petit, E Gomez, A Knoepfli, M Decavele, N Petitpain, F Chabot, A Chaouat
INTRODUCTION: The anti programmed death-1 (PD-1) and the programmed death ligand 1 (PD-L1) antibodies are used as immunotherapies in the treatment of many solid tumours. Cases of interstitial pneumonitis induced by anti PD-1 have been widely described, but there are fewer data with anti PD-L1. Avelumab is a new immunotherapy of the anti PD-L1 class. CASE REPORT: A 66-year-old woman, ex-smoker, had been treated with avelumab and axitinib since November 2016 for renal cell cancer...
October 11, 2018: Revue des Maladies Respiratoires
Adrian C Bateman
This mini review describes some of the key interactions between cancer cells and the immune system. This includes the concept of tumour cell immunosurveillance, mechanisms of immune evasion by tumour cells and some of the novel immunology-based anticancer therapies that have recently been introduced. The latter are also set into the context of the enlarging spectrum of immunohistochemistry-based and molecular testing that can now be performed on formalin-fixed and paraffin-embedded tissues for predicting response to both well-established and newly developed agents...
October 1, 2018: Journal of Clinical Pathology
Isobel Dobbin-Sears, Janet Roberts, Darren D O'Rielly, Proton Rahman
Psoriatic arthritis (PsA) is an inflammatory arthritis that commonly occurs with psoriasis and is attributed to genetic, immunologic and environmental factors. The T-helper (Th)-17 pathway and the interleukin (IL)-23/IL-17 axis have become prominent players in PsA and considerably increased our understanding of disease pathogenesis. In this review article, we will focus on the emerging role of IL-12/23 and its blockade, in the pathogenesis and management of PsA as well as of psoriasis and inflammatory bowel disease...
October 2018: Therapeutic Advances in Chronic Disease
David O Eyarefe, David I Kuforiji, Theophilus A Jarikre, Benjamin O Emikpe
Electrosurgery reduces surgical bleeding, and delayed wound healing. This study evaluated comparative incisional wound healing potential of honey in wound created with electroscalpel and cold scalpel. The study used twelve (12) adult male albino rats (130 ± 20 g), randomly grouped into Electro-cautery (n = 6) and Cold scalpel (n = 6). Each rat had three full thickness (6 mm diameter) skin wounds (a, b and c) created on its dorsum with either Electroscalpel (ES) or Cold blade scalpel (CS), and treated topically with Silver sulphadiazine (SSD, wound a), untreated (control, wound b) and Bee honey (H, wound c)...
December 2017: International Journal of Veterinary Science and Medicine
Gregory M Woods, Samantha Fox, Andrew S Flies, Cesar D Tovar, Menna Jones, Rodrigo Hamede, David Pemberton, A Bruce Lyons, Silvana S Bettiol
The Tasmanian Devil, a marsupial carnivore, has been restricted to the island state of Tasmania since its extinction on the Australian mainland about three thousand years ago. In the past two decades, this species has experienced severe population decline due to the emergence of devil facial tumour disease (DFTD), a transmissible cancer. During these twenty years, scientists have puzzled over the immunological and evolutionary responses by the Tasmanian devil to this transmissible cancer. Targeted strategies in population management and disease control have been developed as well as comparative processes to identify variation in tumor and host genetics...
September 25, 2018: Integrative and Comparative Biology
L V Brown, E A Gaffney, J Wagg, M C Coles
The application of in-silico modelling is beginning to emerge as a key methodology to advance our understanding of mechanisms of disease pathophysiology and related drug action, and in the design of experimental medicine and clinical studies. From this perspective, we will present a non-technical discussion of a small number of recent and historical applications of mathematical, statistical and computational modelling to clinical and experimental immunology. We focus specifically upon mechanistic questions relating to human viral infection, tumour growth and metastasis and T cell activation...
September 2018: Clinical and Experimental Immunology
Elizabeth Ahern, Mark J Smyth, William C Dougall, Michele W L Teng
Recognizing that the transformative effects of immunotherapy are currently limited to a minority of patients with cancer, research efforts are increasingly focused on expanding and enhancing clinical responses by combining immunotherapies; the repurposing of existing drugs is an attractive approach, given their well-characterized safety and pharmacokinetic profiles. Receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were initially described in the context of T cell-dendritic cell interactions; however, the discovery of an obligate role of RANK signalling in osteoclastogenesis led to the development of the anti-RANKL antibody denosumab for antiresorptive indications, including bone metastases...
September 19, 2018: Nature Reviews. Clinical Oncology
Sofia Thomaidou, Arnaud Zaldumbide, Bart O Roep
β-cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduction of the general protein translation rate, increased production of endoplasmic reticulum chaperones and the initiation of degradation by activation of the ER associated degradation pathway (ERAD) in which newly synthetized proteins are ubiquitinylated and processed through the proteasome...
September 2018: Diabetes, Obesity & Metabolism
Valentina Damato, Bettina Balint, Anne-Kathrin Kienzler, Sarosh R Irani
An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody-mediated movement disorders, and outline increasingly well-established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation...
September 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Sterre T Paijens, Ninke Leffers, Toos Daemen, Wijnand Helfrich, H Marike Boezen, Ben J Cohlen, Cornelis Jm Melief, Marco de Bruyn, Hans W Nijman
BACKGROUND: This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials...
September 10, 2018: Cochrane Database of Systematic Reviews
M Setshedi, M Andersson, M M Kgatle, L Roberts
Hepatocellular carcinoma (HCC), as the fifth most diagnosed cancer in the world and the third leading cause of death, is a global health concern. Research stimulated by the dismal prognosis of HCC has led to significant advances in the understanding of its aetio-pathogenesis. Dysregulation of genetic, epigenetic and signalling pathways as well as tumour immunological escape mechanisms are implicated in the development of HCC. This review summarises the current knowledge of these mechanisms and argues that it is only through further understanding of their role in hepatocarcinogenesis, that new effective therapies can be developed...
August 8, 2018: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Pēteris Alberts, Andra Tilgase, Agnija Rasa, Katrīna Bandere, Dite Venskus
Oncolytic viruses are a fast-developing cancer treatment field. Numerous viruses have been tested in clinical trials and three are approved. The first, Rigvir, is an immunomodulator with anti-tumour effect for treatment of melanoma, local treatment of skin and subcutaneous metastases of melanoma, for prevention of relapse and metastasis after radical surgery registered in Latvia, Georgia, Armenia and Uzbekistan. The aim of the present review is to summarize the development of Rigvir. Approximately 60 viruses were screened preclinically...
October 15, 2018: European Journal of Pharmacology
Arthur Dyer, Richard Baugh, Suet Lin Chia, Sally Frost, Iris, Egon J Jacobus, Hena Khalique, Tzveta D Pokrovska, Eleanor M Scott, William K Taverner, Len W Seymour, Janet Lei
The 11th International Oncolytic Virus Conference (IOVC) was held from April 9-12, 2018 in Oxford, UK. This is part of the high-profile academic-led series of meetings that was started back in 2002 by Steve Russell and John Bell, with most of the previous meetings being held in North America (often in Banff). The conference brought together many of the major players in oncolytic virotherapy from all over the world, addressing all stages of research and development-from aspects of basic science and cellular immunology all the way through to early- and late-phase clinical trials...
September 4, 2018: Cancer Gene Therapy
Margherita Ratti, Andrea Lampis, Jens C Hahne, Rodolfo Passalacqua, Nicola Valeri
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups...
November 2018: Cellular and Molecular Life Sciences: CMLS
Daniel Eyraud, Benjamin Granger, Armelle Bardier, Yann Loncar, GaËlle Gottrand, Gilles Le Naour, Jean-Michel Siksik, Jean-Christophe Vaillant, David Klatzmann, Louis Puybasset, Frederic Charlotte, Jeremy Augustin
Cancer research has moved from investigating tumour cells to including analysis of the tumour microenvironment as well. The aim of this study was to assess the cellular infiltrate of colorectal cancer (CRC) using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). TMA slides from 31 CRC patients were immunostained for forkhead box protein 3 (FOXP3) and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) at four sites: centre (C) and invasive front (F) of the tumour, proximal non-metastatic draining lymph node (N-), tumour-draining lymph node with metastasis (N+) and healthy mucosa at 10 cm from the cancer (M)...
August 27, 2018: Pathology
Xiao-Hua Luo, Qingda Meng, Martin Rao, Zhenjiang Liu, Georgia Paraschoudi, Ernest Dodoo, Markus Maeurer
Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen-specific CD8+ T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this 'memory T-cell inflation' phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life...
August 11, 2018: Immunology
J M Braga Diniz, M C Espaladori, M E Souza E Silva, L C N Brito, L Q Vieira, A P Ribeiro Sobrinho
AIM: To evaluate the mRNA expression levels of the cytokines interferon-γ, tumour necrosis factor-α, interleukin (IL)-1β, IL-10, IL-6, VEGF, and AGT and the chemokine CCL2/MCP-1 in periapical interstitial fluid associated with root canal infections before and after the reduction of the bacterial load using a cleaning procedure. METHODOLOGY: The case group included 11 patients with chronic liver disease, and the control group included 11 healthy patients. Clinical samples were taken from teeth with pulp necrosis...
August 8, 2018: International Endodontic Journal
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
Emma Ahlén Bergman, Ciputra Adijaya Hartana, Markus Johansson, Ludvig B Linton, Sofia Berglund, Martin Hyllienmark, Christian Lundgren, Benny Holmström, Karin Palmqvist, Johan Hansson, Farhood Alamdari, Ylva Huge, Firas Aljabery, Katrine Riklund, Malin E Winerdal, David Krantz, A Ali Zirakzadeh, Per Marits, Louise K Sjöholm, Amir Sherif, Ola Winqvist
BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies...
August 3, 2018: Clinical Epigenetics
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