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

Phantomatic Road Works in Poland: A View from a Dashboard Cam

Correct signage belongs to critical factors affecting road traffic safety. During a naturalistic driving study in Poland major mistakes associated with signage were noticed and analysed: road works were announced and speed limits were reduced from 120 km/h to 70−80 km/h, but no road construction could be found. Measurements of drivers’ speed showed their complete disregard of the limitations: average speed of light vehicles remained at 113 km/h and lorries at 88 km/h. Assessment of the encountered 683 road signs revealed 12.5% of them to be inadequate (10.9% falsely informed drivers). Evaluation of contrast ratio of road markings (their replacement was the claimed reason for road work) showed low values both before and after re-placement (Weber contrast 0.6). It is hypothesised that erroneous road signage and its contradiction with the visible road features are contributing to the permanent disobedience of traffic rules in Poland and are decreasing road safety

Glass Beads for Road Markings: Surface Damage and Retroreflection Decay Study

Road markings must be reflectorised with glass beads to be visible to drivers at night, retro-reflecting light from vehicle&rsquo;s headlights, which is critical for road safety. Four commonly used types of glass beads were evaluated in a laboratory setting for retroreflectivity and their surfaces were analysed using optical and scanning electron microscopy. The glass beads were subjected to abrasion and a visual correlation was sought between the measured retroreflectivity and the surface damage. Scratching the glass bead surface with corundum in a rotary drum resulted in major differences in the rates of damage development, depending on the type of the glass beads, and it could be correlated with the rate of retroreflectivity decay. The relative results from abrasion testing were confirmed under tyre action during a turntable evaluation. Based on the outcomes of these tests, service lives, defined as maintaining appropriately high retroreflectivity, were predicted and used to calculate the consumption of raw materials&mdash;the basic sustainability parameter. It was shown that the use of &lsquo;premium&rsquo; glass beads, enhanced with TiO2 and made in a proprietary process, provided the road marking system characterised by the lowest long-term consumption of resources

Visibility of flat line and structured road markings for machine vision

Road markings are equally needed for human drivers and for machine vision equipment; their visibility demands high contrast ratio. Particularly difficult is achieving visibility under the conditions of wetness at night and in the presence of glare from an oncoming vehicle. A field evaluation of visibility by camera and by LiDAR was done on two types of road markings that were applied as pedestrian crossing: flat lines with typical retroreflectivity and structured lines with high retroreflectivity – thus, extreme cases were assessed. The measured camera contrast ratio dropped meaningfully in the presence of moisture in case of flat line markings, but remained high in case of structured markings that facilitated moisture drainage. Glare was detrimental to visibility, bringing it to almost naught regardless of the type of road markings. Simultaneous evaluation with LiDAR showed profound differences under the conditions of moisture: while the response from flat line markings dropped to nil (recovery time >20 s after wetting), the structured markings continuously provided meaningful response. This outcome proves that for reliable guiding by machine vision, as well as for human drivers, structured road markings that facilitate water drainage should be used. For dependable steering by machine vision equipment under adverse conditions, a combination of LiDAR and camera is seen as necessary