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

Bridging Culture, Tourism, and Literature: The Short Videos of Saramago's Small Memories of Azinhaga

A arte, conforme definida por Leo Tolstoi (2013), é a atividade pela qual uma pessoa, tendo experimentado uma emoção, transmite-a intencionalmente a outros. A forte ligação entre o enquadramento geográfico e experiências do autor, despoleta a imaginação do leitor e a vontade de viver na primeira pessoa as experiências. Algumas obras literárias e autores que estimularam os leitores a viajar, por exemplo Stratford-upon-Avon, de William Shakespeare, contribuem para o desenvolvimento local. Outros artistas e formas de arte também exercem o mesmo efeito, César Manrique em Lanzarote com pinturas, esculturas e arquitetura, ou o livro de John Ronald Reuel Tolkien através do filme Senhor dos Anéis promovendo a Nova Zelândia. Turismo cinematográfico ou turismo induzido por filmes é definido como qualquer viagem motivada por cenário com o objetivo de visitação. Nem todos os turistas cinematográficos são motivados da mesma forma, alguns são motivados por cenário, circunscrito e específico, enquanto generalistas visitam regiões ou países (Gürkaya, 2010). O estudo atual visa desenvolver 8 curtas-metragens da obra literária As Pequenas Memórias (2006) do Prémio Nobel José Saramago, onde o autor descreve o seu local de nascimento e experiências da juventude. Este trabalho mais do que a expressão de arte audiovisual visa promover o turismo cultural através uma de ampla estratégia integrada de turismo regional. O potencial deste turismo para o desenvolvimento ainda não atingiu a maturidade. Todos os tipos de turismo são efémeros, assim como os filmes, pelo que qualquer estratégia desenhada que contempla tais soluções necessita de uma reinvenção regular a fim de garantir a sua sustentabilidade.Art, as defined by Leo Tolstoy is the “the activity by which a person, having experienced an emotion, intentionally transmits it to others”. The strong connection between geographic setting and the author’s experiences, triggers the imagination of the reader and the will to experience it thyself. Some of literary works and authors that stimulated readers to travel, for example William Shakespeare’s Stratford-upon-Avon, promoted tourism and local development. Other artists and forms of Art also exert the same effect, César Manrique in Lanzarote with paintings, sculptures and architecture, or the book of John Ronald Reuel Tolkien reaching glory through the film Lord of the Rings promoting New Zealand. Film-tourism or film-induced tourism is defined as any journey to a destination with the purpose of visiting a known film location. Not all film tourists are motivated in the same way, some are motivated by location, specific smaller areas, whereas other generalists visit regions or countries (Aylin Gürkaya, 2010). The current study aims to develop 8 short movies from the Nobel’s prize Saramago literary work “Short memories of Azinhaga” where the author describes his birthplace and youth experiences. This work more than an audio-visual art expression aims to promote regional cultural tourism as a broad integrated regional tourism strategy. The potential of these types of tourism for business and regional development, has yet to reach maturity. All types of tourism are ephemeral, as are films, therefore any drawn strategy contemplating such solutions needs regular reinventing to guarantee sustainability.info:eu-repo/semantics/publishedVersio

Increased Production of Pathogenic, Airborne Fungal Spores upon Exposure of a Soil Mycobiota to Chlorinated Aromatic Hydrocarbon Pollutants

ABSTRACT Organic pollutants are omnipresent and can penetrate all environmental niches. We evaluated the hypothesis that short-term (acute) exposure to aromatic hydrocarbon pollutants could increase the potential for fungal virulence. Specifically, we analyzed whether pentachlorophenol and triclosan pollution results in the production of airborne fungal spores with greater virulence than those derived from an unpolluted (Control) condition. Each pollutant altered the composition of the community of airborne spores compared to the control, favoring an increase in strains with in vivo infection capacity (the wax moth Galleria mellonella was used as an infection model). Fungi subsisting inside larvae at 72 h postinjection with airborne spore inocula collected in polluted and unpolluted conditions exhibited comparable diversity (mainly within Aspergillus fumigatus). Several virulent Aspergillus strains were isolated from larvae infected with the airborne spores produced in a polluted environment. Meanwhile, strains isolated from larvae injected with spores from the control, including one A. fumigatus strain, showed no virulence. Potential pathogenicity increased when two Aspergillus virulent strains were assembled, suggesting the existence of synergisms that impact pathogenicity. None of the observed taxonomic or functional traits could separate the virulent from the avirulent strains. Our study emphasizes pollution stress as a possible driver of phenotypic adaptations that increase Aspergillus pathogenicity, as well as the need to better understand the interplay between pollution and fungal virulence. IMPORTANCE Fungi colonizing soil and organic pollutants often meet. The consequences of this encounter constitute an outstanding question. We scrutinized the potential for virulence of airborne fungal spores produced under unpolluted and polluted scenarios. The airborne spores showed increased diversity of strains with higher infection capacity in Galleria mellonella whenever pollution is present. Inside the larvae injected with either airborne spore community, the surviving fungi demonstrated a similar diversity, mainly within Aspergillus fumigatus. However, the isolated Aspergillus strains greatly differ since virulence was only observed for those associated with a polluted environment. The interplay between pollution and fungal virulence still hides many unresolved questions, but the encounter is costly: pollution stress promotes phenotypic adaptations that may increase Aspergillus pathogenicity