Skovgilmore6013

High-grade serous ovarian cancer (HGSC), the principal cause of death from gynecologic malignancies in the world, has not significantly benefited from advances in cancer immunotherapy. Although HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. The goal of this study was to establish the global landscape of HGSC tumor-specific antigens (TSA) using a mass spectrometry pipeline that interrogated all reading frames of all genomic regions. In 23 HGSC tumors, we identified 103 TSAs. Classic TSA discovery approaches focusing only on mutated exonic sequences would have uncovered only three of these TSAs. Other mutated TSAs resulted from out-of-frame exonic translation (n = 2) or from noncoding sequences (n = 7). One group of TSAs (n = 91) derived from aberrantly expressed unmutated genomic sequences, which were not expressed in normal tissues. These aberrantly expressed TSAs (aeTSA) originated primarily from nonexonic sequences, in particular intronic (29%) and intergenic (22%) sequences. Their expression was regulated at the transcriptional level by variations in gene copy number and DNA methylation. Although mutated TSAs were unique to individual tumors, aeTSAs were shared by a large proportion of HGSCs. Taking into account the frequency of aeTSA expression and HLA allele frequencies, we calculated that, in Caucasians, the median number of aeTSAs per tumor would be five. We conclude that, in view of their number and the fact that they are shared by many tumors, aeTSAs may be the most attractive targets for HGSC immunotherapy. ©2020 American Association for Cancer Research.The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of CTLA-4-blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy. Copyright ©2020, American Association for Cancer Research.INTRODUCTION Poor diet is a leading risk factor for non-communicable diseases and costs the National Health Service £5.8 billion annually. Product placement strategies used extensively in food outlets, like supermarkets, can influence customers' preferences. Policy-makers, including the UK Government, are considering legislation to ensure placement strategies promote healthier food purchasing and dietary habits. High-quality scientific evidence is needed to inform future policy action. This study will assess whether healthier placement strategies in supermarkets improve household purchasing patterns and the diets of more than one household member. METHODS AND ANALYSES This natural experiment, with a prospective matched controlled cluster design, is set in discount supermarkets across England. The primary objective is to investigate whether enhanced placement of fresh fruit and vegetables improves household-level purchasing of these products after 6 months. Secondary objectives will examine (1) differences in bmitted for publication in peer-reviewed scientific journals and shared with policy-makers. TRIAL REGISTRATION NUMBER NCT03573973; Pre-results. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.INTRODUCTION Minimally invasive surgery in urology has grown considerably in application since its initial description in the early 1990s. Herein, we present the protocol for a systematic review and meta-analysis comparing open versus robotic urological oncological surgery for various clinically relevant outcomes, as well as to assess their comparative penetrance over the past 20 years (2000-2020). METHODS AND ANALYSIS We will document the penetrance of robotic versus open surgery in the urological oncological field using a national database.Second, we will perform a systematic review and meta-analysis of all published full-text English and non-English language articles from Pubmed, Scopus and Web of Science search engines on surgical treatment of localised prostate, bladder, kidney and testis cancer published between 1st January 2000 to 10th January 2020. We will focus on the highest-volume urological oncological surgeries, namely, radical prostatectomy, radical cystectomy, partial nephrectomy, radical nephrical surgery based on all the available literature. These aggregate data will help physicians better advise patients seeking surgical care for urological cancers. PROSPERO REGISTRATION NUMBER CRD42017064958. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Lateral compression type 1 (LC1) pelvic fractures are the most common type of pelvic fracture. The majority of LC1 fractures are considered stable. Fractures where a complete sacral fracture is present increases the degree of potential instability and have the potential to displace over time. Non-operative management of these unstable fractures may involve restricted weight bearing and significant rehabilitation. Frequent monitoring with X-rays is also necessary for displacement of the fracture. Operative stabilisation of these fractures may be appropriate to prevent displacement of the fracture. This may allow patients to mobilise pain-free, quicker. METHODS AND ANALYSIS The study is a feasibility study to inform the design of a full definitive randomised controlled trial to guide the most appropriate management of these injuries. check details Participants will be recruited from major trauma centres and randomly allocated to either operative or non-operative management of their injuries. A variety of outcome instruments, measuring health-related quality of life, functional outcome and pain, will be completed at several time points up to 12 months post injury.