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

Indian silverwork of the Southwest, illustrated /

[v. 1]. Bridles -- [v. 2]. Band bracelets, filed and stamped -- [v. 3]. Band bracelets embossed.Mode of access: Internet

Identity is an Infinite Now: Being Instead of Becoming Gallina

Archaeological research on the Gallina (AD 1100–1300) inhabitants of the region west of the Rio Chama and centered on the Llaves valley has focused on constructing a culture history and examining functional characteristics of artifacts and architecture. Limited research has attempted to understand who the residents of the Gallina heartland were. In this article, using new findings and historical contexts, we argue that the Gallina people had a complicated identity forged around resistance and a deep connection to their past. To better understand them we need to move past previous binary categories used to describe them and perceive them not as isolated or connected, aggressors or victims, traditionalists or innovators, but as an intersectional mix of these axes of identity.La investigación arqueológica sobre los habitantes Gallina (1100–1300 d. C.) de la región oeste del Río Chama, focalizada en el valle de Llaves, se orientó en la construcción de una historia cultural y el análisis de las características funcionales de los artefactos y la arquitectura. De hecho, han sido escasas las investigaciones que han intentado entender quiénes eran los residentes del Gallina. En este artículo, utilizando nuevos hallazgos y contextos históricos, argumentamos que los grupos Gallina tuvieron una identidad compleja, forjada en torno a la resistencia y a una profunda conexión con su historia. Asimismo, para entenderlas necesitamos movernos más allá de las tradicionales categorías binarias usadas para interpretarlos y percibirlos como aislados o conectados, violentos o víctimas, tradicionalistas o inventores, y en cambio, como una mezcla que abarca todos estos ejes de identidad.Archaeology of the America