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

Skin in the game: the use of sensing smart fabrics in tennis costume as a means of analyzing performance

Abstract Underlying the surface decoration and cut of contemporary tennis costume is a fabric that enacts its own performance and studies the athlete who wears it. Whilst designers such as Teddy Tinling created tennis costumes that brought glamour and theatrical flair to the player’s performance, modern sports companies are increasingly using costume to approach human performance from a big data perspective. In the late nineteenth century, women playing tennis wore corsets and long skirts which impeded movement; today, the top players utilize fabric science that enables costume to control and record the temperature, sweat and muscle movement of the performer, whilst also presenting a vehicle to showcase their personality through their aesthetic choices. Smart fabrics allow for greater and more precise control over how our bodies perform, and they similarly alter our understanding of materiality and bodily presence with regards to fashion. The use of smart fabrics in sports, where the patterns of data collected by the costume visually and numerically display the conditions of the player/performance, holds potential for the ways in which we interrogate the interrelationship of clothing and performance across a range of arenas. For fashion research this means it is now possible not just to look at a costume but to look through it, via biometric capture, to a performance realized in data space. It is this duality of costume both in and as performance space that provokes this article to raise questions about the changeable nature of smart clothing and its relationship to the sporting body

Opening the Door to Old Town Key West: Physical Thresholds in the Storied Narrative of the Conch Train Tour

Dubbed “The Nation\u27s Storyteller,” Historic Tours of America provides historically oriented tourist experiences through the operation of storytelling trolley and train tours. I argue that to understand the narrative potential of such tours, it is important to step back from the tour as staged attraction and examine its position as “threshold” in the interplay between place and story. In this article, I analyze the script from the Conch Train Tour in Key West in order to examine how the storytelling of the tour guide augments the experience of viewing buildings. In this example, the eye is directed to specific features of various doorways as a means of introducing visitors to historically defining moments in the island’s past. Drawing on Bakhtin’s theory of the chronotope, I explain how points of physical access into a building are used as points of access to that building’s social pasts. I conclude that the narrative strategies of this particular sightseeing tour highlight a relationship between spatial augmentation and architectural thresholds as a valuable way to explore the storytelling of place

Unwrapping the virtual reality mummy : an investigation of the chronotopes underpinning the interpretation of a virtual reality artefact

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