Billy Yank On The Northern Plains: The Lives Of Union Soldiers On The Minnesota-Dakota Frontier From The Great Sioux Uprising To 1866

This thesis will tell the generally forgotten story of the Civil War era soldiers on the Minnesota-Dakota frontier who fought in the Great Sioux Uprising from 1862 to 1865. It will also compare the frontier soldiers’ campaign experience with the experiences of Bell Irvin Wiley’s Civil War ‘\u27Billy Yanks.” This thesis covers enlistment procedures, food, clothing, shelter, discipline, disease, boredom, combat, the “galvanized” Yankees, the Dakota landscape, and the role of the cavalry. This story of the frontier soldiers’ expeditions against the Sioux on the northern plains is told using direct quotations from frontier soldiers’ diaries and manuscripts, along with United States government records, the Fort Rice publication. Frontier Scout, and various secondary sources. Most frontier “Billy Yanks” enlisted to fight in the Civil War; instead, they pursued the Sioux Indians across Dakota Territory on expeditions with generals Henry H. Sibley and Alfred T. Sully. In general, the experiences of these frontier soldiers were remarkably similar to those of Civil War soldiers. Subtle differences did exist, but for the most part, frontier soldiers shared common bonds with other Civil War era fighting men, such as life at military posts, boredom, and disease. However, frontier soldiers experienced a pronounced difference from their Civil War comrades in the combat and landscape they faceu, fighting Native Americans in th

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