System and human needs : comparative analysis of a systems framework for finding indicators for sustainable development with a theory of fundamental human need

This thesis represents a contribution to methods of conceptualising the current environmental and social problems dominating the world, and helping direct developmental paths to lead to a better world. The method analysed is a systems theoretical framework for defining indicator sets for sustainable development, developed by Hartmut Bossel. The phrase 'sustainable development' is based on grounded principles and represents an ethical guide to direct action for a better world for all, including future generations. 'Systems thinking' is a useful tool for conceptualising complex situations, such as the interrelated environmental, economic, social and institutional aspects of development'. Indicators are required to tell us the states and changing trends of systems that are important to us. Bossel's framework suggests that each of the essential subsystems of the globe, namely the natural, support (economy and infrastructure) and human subsystems, must be sustainable for global development to be viable in the long term. This thesis focuses on the human subsystem and compares Bossel's systems theoretical framework with Max-Neef's theory of fundamental human need. Based on systems theory, as discussed by Bossel, every system has 'orientors' (needs) which require satisfying if the system is to be viable in the long term. Fundamental human needs categories have been independently identified by Max-Neef and in the human context seem to match the system 'orientors'. These system 'orientors' and human needs are compared and analysed in a sustainable development context. The thesis attempts to determine what the theory of fundamental human need can contribute to the generic systems framework for finding indicators for a goal of sustainable development. The analysis shows that human needs do indeed match well with system needs in the human context, although not exactly as previously identified. Some differences between the frameworks are identified, and their significance is determined by a practical framework test of defining indicator sets for the city of Christchurch. The framework differences identified do not appear significant for the goal of defining social indicators for sustainable development. However, the theory of fundamental human need adds important insight by identifying that needs can be understood in a continuing subjective dialectic relationship between needs and satisfiers. The framework enables a critical analysis of the 'negative' satisfiers affecting a society so that the actualisation of needs becomes not only the goal but the 'motor of development'

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