Subsistence Patterns as Markers of Cultural Exchange: European and Taino Interactions in the Dominican Republic

Thesis (PhD) - Indiana University, Anthropology, 2006Although the stories of Christopher Columbus's voyages to the New World are well known, the daily life of his sailors and the indigenous people they met are not as clearly understood. This research investigates the reciprocal influence of cultures in contact through an analysis of a basic element in the lives of these people: food. Although documentary records and paleoenvironmental studies can explain which plants and animals were gathered, these sources suffer from biases. For instance, at the site of La Isabela in the Dominican Republic, European chroniclers were motivated by specific agendas colored by pride, cultural superiority, and salesmanship. They rarely recorded the activities of any but the elites of either the colonists or the Tainos encountered there. Also, because the faunal and floral remains are often poorly preserved or statistically inconclusive, an archaeological reconstruction of the typical diet is less than accurate. To learn more about the interactions between the native people and the explorers, comparisons were made of domestic ceramic artifacts and the associated food residue recovered from the La Isabela colony and the surrounding indigenous villages. Further, absorbed organic residue analysis is employed to resolve many questions surrounding the interactions of cultures in such an unprecedented arrangement. The method uses gas chromatography - mass spectrometry to identify the preserved organic molecules extracted from within walls of domestic pottery. By evaluating specific fatty acids and lipid constituents from both native and colonial ceramics, the research distinguishes broad food categories as well as various families of plants and animals that were consumed. Contrary to the established paradigm which holds that the Spanish starved and the indigenous people were completely destroyed, the food residue reflects similar patterns of sustenance and vessel use between the groups, suggesting a more complex pattern of cultural exchange. While this method has its limitations, especially with regards to the reconstruction of cuisines exploiting a wide variety of resources and the recovery of residues from sherds deposited in tropical environments, the research can supply valuable information on the little understood dietary practices of colonists and their hosts

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