31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Combining Big Data Analysis to Study the Relationship between the Tone of CSR Reports and Information Asymmetry

Big data mining and analytics help uncover hidden patterns and correlations in business. It serves as the optimal tool to interpret the behavior of companies in specific environments. Built on the large amount of data obtained from various sources, this paper examines the relationship between the tone of corporate social responsibility(CSR) reports and the degree of information asymmetry between investors and managers. Python software is used for data collection, text analysis, and word frequency statistics. The results show that the tone of the social responsibility report reduces the degree of information asymmetry, indicating that the tone of the social responsibility report has an incremental information effect. Further analysis shows that the tone of CSR reports significantly reduces information asymmetry in companies with optimistic forecasts and high media attention

Transfer learning to decode brain states reflecting the relationship between cognitive tasks

Transfer learning improves the performance of the target task by leveraging the data of a specific source task: the closer the relationship between the source and the target tasks, the greater the performance improvement by transfer learning. In neuroscience, the relationship between cognitive tasks is usually represented by similarity of activated brain regions or neural representation. However, no study has linked transfer learning and neuroscience to reveal the relationship between cognitive tasks. In this study, we propose a transfer learning framework to reflect the relationship between cognitive tasks, and compare the task relations reflected by transfer learning and by the overlaps of brain regions (e.g., neurosynth). Our results of transfer learning create cognitive taskonomy to reflect the relationship between cognitive tasks which is well in line with the task relations derived from neurosynth. Transfer learning performs better in task decoding with fMRI data if the source and target cognitive tasks activate similar brain regions. Our study uncovers the relationship of multiple cognitive tasks and provides guidance for source task selection in transfer learning for neural decoding based on small-sample data

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization

Fungal diversity notes 1512–1610: taxonomic and phylogenetic contributions on genera and species of fungal taxa

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