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

The Use of Lidar Data and VHR Imagery to Estimate the Effects of Tree Roots on Shallow Landslides Assessment

The study of geo-hazards has been benefited from the technological advances in the field of Remote Sensing (RS) techniques as the ALS (Airborne Laser Scanners) Systems with Very High Resolution (VHR) cameras. Recently, the LiDAR (Light Detection and Ranging) is an active sensor technique used for a variety of geoscientific applications including slope monitoring to retrieve ground surface displacements at high spatial resolution. Additionally, LiDAR has been widely used in order to collect high-resolution information on forests structure for the determination and characterization of vegetation cover due its ability to capture multiple returns and to reach the ground, even in forested areas, allowing the generation of Digital Terrain Models (DTMs) for the estimation of forest variables. In this paper, a LiDAR dataset and VHR imagery from aerial survey was used in the southwest zone of Medellín City-Colombia where the most frequent landslides are shallow and triggered by rainfall. Slopes with gradients up to 30% on residual soils characterize the study area, having about of 30% of forest cover consisting predominantly of Eucalyptus and Coniferous forests. For the estimation of the tree roots effects on the shallow landslides assessment on a natural slope, interpolation processes were developed from the LiDAR 3D point cloud, obtaining DTMs of 1 m-pixel. Additionally, orthophotos with the same spatial resolution were acquired in the aerial campaign. The proposed workflow was implemented on a GIS platform, and considers the extraction of the tree heights by generating a Canopy Height Model (CHM), while for the delineation of the tree crown a process of image segmentation was developed. Once the vegetation has been characterized using LiDAR products and dendrometric relationships, the Limit Equilibrium Method (LEM) was used to evaluate slope stability considering the effect of vegetation (trees). The results indicate that the proposed workflow allows to obtain adequate stability indicators for the estimation of tree roots contribution and additionally, this RS technique allows saving resources in this kind of analysis. © Published under licence by IOP Publishing Ltd

Recommendations for Future Efforts in RANS Modeling and Simulation

The roadmap laid out in the CFD Vision 2030 document [1] suggests that a decision to move away from RANS research needs to be made in the current timeframe (around 2020). This paper outlines industry requirements for improved predictions of turbulent flows and the cost-barrier that is often associated with reliance on scale resolving methods. Capabilities of RANS model accuracy for simple and complex flow fields are assessed, and modeling practices that degrade predictive accuracy are identified. Suggested research topics are identified that have the potential to improve the applicability and accuracy of RANS models. We conclude that it is important that some part of a balanced turbulence modeling research portfolio should include RANS efforts