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

An Observational Study of Dyspnea in Emergency Departments: The Asia, Australia, and New Zealand Dyspnea in Emergency Departments Study ( AANZDEM )

International audienceObjectives: The objective was to describe the epidemiology of dyspnea presenting to emergency departments (EDs) in the Asia-Pacific region, to understand how it is investigated and treated and its outcome.Methods: Prospective interrupted time series cohort study conducted at three time points in EDs in Australia, New Zealand, Singapore, Hong Kong, and Malaysia of adult patients presenting to the ED with dyspnea as a main symptom. Data were collected over three 72-hour periods and included demographics, comorbidities, mode of arrival, usual medications, prehospital treatment, initial assessment, ED investigations, treatment in the ED, ED diagnosis, disposition from ED, in-hospital outcome, and final hospital diagnosis. The primary outcomes of interest are the epidemiology, investigation, treatment, and outcome of patients presenting to ED with dyspnea.Results: A total of 3,044 patients were studied. Patients with dyspnea made up 5.2% (3,105/60,059, 95% confidence interval [CI] = 5.0% to 5.4%) of ED presentations, 11.4% of ward admissions (1,956/17,184, 95% CI = 10.9% to 11.9%), and 19.9% of intensive care unit (ICU) admissions (104/523, 95% CI = 16.7% to 23.5%). The most common diagnoses were lower respiratory tract infection (20.2%), heart failure (14.9%), chronic obstructive pulmonary disease (13.6%), and asthma (12.7%). Hospital ward admission was required for 64% of patients (95% CI = 62% to 66%) with 3.3% (95% CI = 2.8% to 4.1%) requiring ICU admission. In-hospital mortality was 6% (95% CI = 5.0% to 7.2%).Conclusion: Dyspnea is a common symptom in ED patients contributing substantially to ED, hospital, and ICU workload. It is also associated with significant mortality. There are a wide variety of causes however chronic disease accounts for a large proportion

Teaching Bioeconomics

Bioeconomics is a relatively young field that uses an expanded microeconomics to examine animal behavior, human behavior, and animal and human social institutions. A voluminous literature is rapidly accumulating. There are as yet no standard textbooks, but there are several excellent books and/or articles that can be used in combination with videos and other aids to make a course that students will enjoy and that teachers can use to advance the frontiers of scholarship in economics and biology. Copyright Springer 2005altruism, conflict, cooperation, evolution, game theory, institutions, rationality,