PURPOSE Characterize the role of B-cells on HPV-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations. EXPERIMENTAL DESIGN Tumor RNA sequencing data from over 800 HNSCC and cervical cancer patients, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival. A novel murine model of HPV+ HNSCC was used to study the effects of PD-1 blockade and RT on B-cell activation, differentiation, and clonality including analysis by single-cell RNA sequencing and B-cell receptor sequencing. Human protein microarray was then used to quantify B-cell mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade. RESULTS RNA sequencing identified CD19 and IGJ as novel B-cell prognostic biomarkers for 3-year overall survival (HR = 0.545, p less then 0.001). PD-1 blockade and RT enhance development of memory B-cells, plasma cells, and antigen-specific B-cells. B-cell receptor sequencing found that RT enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA sequencing identified dramatic increases in B-cell germinal center formation after PD- 1 blockade and RT. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade. CONCLUSIONS These findings establish a key role for B-cells in patient outcomes and responses to PD-1 blockade in HPV-associated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B-cells. Copyright ©2020, American Association for Cancer Research.BACKGROUND The objective of this analysis was to examine the association between asthma control (based on Asthma Control Test (ACT) responses) and healthcare resource utilisation (HRU), work productivity and health-related quality of life (HRQoL) among a nationwide sample of US adults with a self-reported diagnosis of asthma and without comorbid chronic obstructive pulmonary disease. METHODS Data were obtained from the 2015 and 2016 self-administered, internet-based National Health and Wellness Surveys. Patients were grouped by ACT score (≤15 poorly controlled; 16-19 partly controlled; 20-25 well-controlled asthma). Study outcomes included HRU (patient-reported healthcare provider visits, emergency department visits and hospitalisations during the previous 6 months); work productivity, measured using the Work Productivity and Activity Impairment-General Health Scale; HRU-associated costs and work productivity loss and HRQoL, measured using EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) and the Short Form Health Surly controlled or poorly controlled asthma (p less then 0.001). CONCLUSIONS The study demonstrates a clear relationship between asthma control and its impact on HRU, costs, work productivity and HRQoL. This will allow for better identification and management of patients with poorly controlled asthma. © 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.Thermo Fisher Scientific announced plans in March to acquire Qiagen in a $11.5 billion deal that could bring morediagnostic offeringsand sample-preparation technologies to one of the world's leading manufacturers of scientific instruments, research services, and laboratory consumables. ©2020 American Association for Cancer Research.Insufficient reactivity against cells with low antigen density has emerged as an important cause of CAR resistance. Little is known about factors that modulate the threshold for antigen recognition. We demonstrate that CD19 CAR activity is dependent upon antigen density and the CAR construct in axicabtagene-ciloleucel (CD19-CD28z) outperforms that in tisagenlecleucel (CD19-4-1BBz) against antigen low tumors. Enhancing signal strength by including additional ITAMs in the CAR enables recognition of low antigen density cells, while ITAM deletions blunt signal and increase the antigen density threshold. Further, replacement of the CD8 hinge-transmembrane (H/T) region of a 4-1BBz CAR with a CD28-H/T lowers the threshold for CAR reactivity despite identical signaling molecules. https://www.selleckchem.com/products/td139.html CARs incorporating a CD28-H/T demonstrate a more stable and efficient immunological synapse. Precise design of CARs can tune the threshold for antigen recognition and endow 4-1BBz-CARs with enhanced capacity to recognize antigen low targets while retaining a superior capacity for persistence. Copyright ©2020, American Association for Cancer Research.Surgery is the only curative option for Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease after adjuvant or first-line platinum therapy corresponds to an increased mutational burden. Recurrent disease is enriched for genetic alterations predicted to activate Mapk/Erk and PI3K/AKT signaling and develops from a monophyletic or polyphyletic origin. Treatment induced genetic bottlenecks lead to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings suggest routine post-treatment sampling may have value in the management of recurrent pancreatic cancer. Copyright ©2020, American Association for Cancer Research.Glaucoma is a leading cause of irreversible visual impairment, and primary angle closure glaucoma (PACG) affects Asians disproportionately. Whereas advances in ocular imaging have identified several anatomical risk factors, our ability to predict PACG still requires considerable improvement. The iris plays a crucial role in the pathophysiology of angle closure disease, either through a mechanical or vascular mechanism. Irises of closed-angle eyes inhibit vastly different structural constituents as compared with those of open-angle eyes, thereby effecting variations in biomechanical properties and iris fluid conductivity. The clinical consequences include a smaller change in iris volume on pupil dilation in closed-angle eyes, thereby bringing the iris and trabecular meshwork closer in apposition. In this review, we summarise the potential role of the iris in the pathogenesis of angle closure disease. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.