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

Marketing analytics : a practical guide to real marketing science / Mike Grigsby.

business bookfair2016xv, 232 pages :"Mike Grigsby provides business analysts and marketers with the marketing science understanding and techniques they need to solve real-world marketing challenges, such as pulling a targeted list, segmenting data, testing campaign effectiveness, and forecasting demand.Assuming no prior knowledge, Marketing Analytics introduces concepts relating to statistics, marketing strategy, and consumer behavior and then works through a series of problems by providing various data modeling options as solutions. By using this format of presenting a problem and multiple ways to solve it, this book both makes marketing science accessible to beginners and aids the more experienced practitioner in understanding the more complex aspects of data analytics to refine their skills and compete more effectively in the workplace"-- Provided by publisher."Marketing Analytics arms business analysts and marketers with the marketing science understanding and techniques they need to solve real-world marketing problems, from pulling a targeted list and segmenting data to testing campaign effectiveness and forecasting demand. Assuming no prior knowledge, this book outlines everything practitioners need to 'do' marketing science and demonstrate value to their organization. It introduces concepts relating to statistics, marketing strategy and consumer behaviour and then works through a series of marketing problems in a straightforward, jargon-free way. It demonstrates solutions for various data modelling scenarios and includes full workings and critical analyses to reinforce the key concepts. By starting with the marketing problem and then sharing a series of data modelling options on how to solve it, Marketing Analytics both makes marketing science accessible for beginners and aids the more seasoned practitioner in getting to grips with the trickier technical aspects of data analytics to refine their marketing skills and toolkit and compete more effectively in the marketplace. About the series: The Marketing Science series makes difficult topics accessible to marketing students and practitioners by grounding them in business reality. Each book is written by an expert in the field and includes case studies and illustrations so marketers can gain confidence in applying the tools and techniques and commission external research"-- Provided by publisher

Materials Education and Research in Art and Design: A New Role for Libraries - Session 4. Designers

Designers respond to issues and synthesize ideas from throughout the day as voices from the field who directly encounter the need for recently graduated students to possess the ability to investigate and interrogate materials

National Geographic : understand civil engineering differently

Our undergraduate civil engineering students have access to a rich and diverse bank of textual and graphical knowledge concerning their chosen profession. However, over a number of decades, commentators have raised concerns that our students have insufficient understanding of the role of civil engineering in society. Indeed, the call for universities to educate ‘global engineers’ emphasises the need for our students to be schooled in the humanities, in parallel with their core computational studies. Unfortunately, engineering students in particular, are not accustomed to regular exploratory reading. This paper considers the use of the National Geographic magazine as a means to ignite our students’ curiosity with the world around them. The results from a pilot study and a content analysis of a number of editions from over a decade shows that this periodical regularly carries themes directly concerning the impact of civil engineering in society, be it political , financial environmental , social or ecological