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

Motherhood Status Moderates the Relationship between Perfectionistic Self-Presentation and Breast Size Dissatisfaction

Perfectionistic self-presentation refers to a desire to create an image of flawlessness in the eyes of the others and has been associated with more negative body image. We extended previous research by examining associations between perfectionistic self-presentation and breast size dissatisfaction, and also examined whether motherhood status moderated this association. A total of 484 Italian women (age M = 40.39, SD = 13.73; mothers n = 53.9%) completed measures of perfectionistic self-presentation (perfectionistic self-promotion, nondisplay of imperfection, and nondisclosure of imperfection) and breast size dissatisfaction. Preliminary analyses indicated that a majority of the sample (69.2%) reported breast size dissatisfaction, with 44.4% and 24.4% desiring larger and smaller breasts, respectively, than they currently had. Only perfectionistic self-promotion and nondisplay of imperfection were significantly correlated with breast size dissatisfaction. Both associations were additionally moderated by motherhood status, with associations being significant in non-mothers but not in mothers. Our findings suggest that motherhood may help decouple the link between perfectionistic self-presentation and breast size dissatisfaction. Future studies should assess whether this effect is due to an enhanced maternal view of breasts that emphasises nurturing and biological functions or a result of weaker investment in sociocultural norms on physical appearance

Writing Truth to Power : Jonas Khemiri’s Work in Stockholm and New York

This article explores the work of Swedish writer Jonas Hassen Khemiri, of partly Tunisian origin, in terms of cultural translation and comparison between Stockholm and New York. I discuss three texts by Khemiri in different writing genres: first, an open letter to Sweden’s Minister of Justice, which went viral in 2013 and was also published in the New York Times , about racial profiling in Stockholm; second, the play I Call My Brothers , written in response to a failed terrorist attack in Stockholm in 2010 and staged in New York; third, the award‐winning novel Everything I Don’t Remember (2016b) selected as a 2016 Times Literary Supplement Book of the Year by Joyce Carol Oates. Why would Khemiri’s open letter, play, and novel that address new issues of power, stereotypes, and physical appearance in Sweden matter in the United States, with its deep‐rooted diversity? The conclusion is that the international success of these pieces has nothing to do with Sweden or an interest in Swedish contemporary life but can be understood as local variations on the global themes of terrorist crimes and racial profiling

Responses of terrestrial ecosystems to temperature and precipitation change: a meta-analysis of experimental manipulation.

16 páginas, 3 figuras, 5 tablas.Global mean temperature is predicted to increase by 2–7 1C and precipitation to change across the globe by the end of this century. To quantify climate effects on ecosystem processes, a number of climate change experiments have been established around the world in various ecosystems. Despite these efforts, general responses of terrestrial ecosystems to changes in temperature and precipitation, and especially to their combined effects, remain unclear. We used metaanalysis to synthesize ecosystem-level responses to warming, altered precipitation, and their combination. We focused on plant growth and ecosystem carbon (C) balance, including biomass, net primary production (NPP), respiration, net ecosystem exchange (NEE), and ecosystem photosynthesis, synthesizing results from 85 studies. We found that experimental warming and increased precipitation generally stimulated plant growth and ecosystem C fluxes, whereas decreased precipitation had the opposite effects. For example, warming significantly stimulated total NPP, increased ecosystem photosynthesis, and ecosystem respiration. Experimentally reduced precipitation suppressed aboveground NPP (ANPP) and NEE, whereas supplemental precipitation enhanced ANPP and NEE. Plant productivity and ecosystem C fluxes generally showed higher sensitivities to increased precipitation than to decreased precipitation. Interactive effects of warming and altered precipitation tended to be smaller than expected from additive, single-factor effects, though low statistical power limits the strength of these conclusions. New experiments with combined temperature and precipitation manipulations are needed to conclusively determine the importance of temperature–precipitation interactions on the C balance of terrestrial ecosystems under future climate conditions.This work was supported by the National Institute of Climatic Change Research, the US National Science Foundation (DEB-0092642), the government of Catalunya (AGAUR 2005PIV00123, Grant SGR2009-458), the Spanish Government (Grants CGL2006- 04025/BOS and Consolider Ingenio Montes CSD2008-00040), and Science Foundation Arizona (GRF 0001-07).Peer reviewe