Compounding the Results: The Integration of Virtual Worlds With the Semantic Web

Over the past 20 years, governmental use of Web-base information and technologies has continually expanded taking advantage of the Web's vast, ever- expanding volumes of browser-accessible information. Now, it infuses two new technologies, the first one espousing a world where semantic-powered applications become knowledgeable assistants for Web users. The second new technology takes a perceivably flat two-dimensional approach to presenting current Web-content and adds a three-dimensional perspective to the presentation. Welcome to the Semantic Web as seen through the eyes of a Virtual World participant, an environment where Web users no longer are browsing for information that is largely static, where Web users interact through their proxies (avatars) query applications (Web agents) soliciting them to collect, filter, verify, correlate and present answers to their queries often in a more visually palatable three-dimensional format. Following a brief overview of these two technologies, this article presents several of the key force drivers behind their evolution and the benefits gleaned from their collective use. Further discussion identifies new methods for visualizing semantic content in virtual worlds. Finally, as with any technological evolution, the merge of these two technologies brings on a whole new set of challenges from a Web userÕs perspective as well as perspectives from technology developers both in academia and government

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

Compounding the Results: The Integration of Virtual Worlds With the Semantic Web

Over the past 20 years governmental use of Web-base information and echnologies has continually expanded taking advantage of the Web's vast ever- xpanding volumes of browser-accessible information. Now it infuses two new echnologies the first one espousing a world where semantic-powered applications ecome knowledgeable assistants for Web users. The second new technology takes a erceivably flat two-dimensional approach to presenting current Web-content and dds a three-dimensional perspective to the presentation. Welcome to the Semantic eb as seen through the eyes of a Virtual World participant an environment where eb users no longer are browsing for information that is largely static where Web sers interact through their proxies (avatars) query applications (Web agents) oliciting them to collect filter verify correlate and present answers to their queries ften in a more visually palatable three-dimensional format. Following a brief verview of these two technologies this article presents several of the key force rivers behind their evolution and the benefits gleaned from their collective use. urther discussion identifies new methods for visualizing semantic content in virtual orlds. Finally as with any technological evolution the merge of these two echnologies brings on a whole new set of challenges from a Web userÕs perspective s well as perspectives from technology developers both in academia and overnment