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

Systems

Mainstream visual psychology presents a ‘sense then infer ’ account of vision that is analogous to the ‘sense then infer ’ processing that characterises the agent intention recognition literature. From ecological psychology comes Gibson’s theory of visual perception that highlights the importance of the environment in explaining the nature of vision and recognition and claims that higher order structures are directly accessible. This theory can be used as the stepping-off point for an account of intention recognition and the means by which it might be modelled. Furthermore, the capacity for virtual environments to be designed ‘agent friendly ’ provides yet another dimension of design freedom. When accompanied by an explicit model of perception the intention recognition problem can be cast as a software design problem. The resulting design patterns provide useful options for modelling intention recognition in intelligent agent systems

Using the UML to model knowledge in agent systems

The UML has been used to model the knowledge required to engineer agent systems. The UML provides mechanisms for modelling the knowledge about a domain, partitioning the knowledge into appropriate packages and providing a means of moving from analysis to design. This paper argues that the UML is a suitable language for knowledge modelling in agent systems and provides details of the techniques and extensions employed. By modifying and applying commonly used mainstream modelling languages such as the UML tool and methodology support for the construction of agent systems can be leveraged from existing practices

An Action Research Report from a Multi-Year Approach to Teaching Artificial Intelligence at the K-6 Level

In Australia, the Scientists-in-Schools program partners professional scientists with teachers from K-12 schools to improve early engagement and educational outcomes in the sciences and mathematics. &nbsp;An overview of the developing syllabus of a K-6 course resulting from the pairing of a senior AI researcher with teachers from a K-6 (primary) school is presented. Now entering its third year, the course introduces the basic concepts, vocabulary and history of science generally and AI specifically in a manner that emphasises student engagement and provides a challenging but age appropriate syllabus. Reflecting on the course at this time provides an action research basis for ongoing maturation of the syllabus, and the paper is presented in that light

Designing perception modules to shape information for agents

The difficulty associated with placing intelligent agents in environments is in part one of designing the means by which they sense their world. If the world is complex, or if the information available in the world is in an inappropriate form, then a mismatch between the information in the environment and the information required by the agent can exist. Practical means of dealing with this mismatch are available but designing the system requires careful modelling. By modelling perception as the module within the agent responsible for sensing and making sense of the environment several advantages are realised. The explicit representation of perception allows consideration of the issues, affords software engineering advantages with respect to the specification and design of systems and is compatible with many accepted definitions of agency