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

Using the Theory of Planned Behavior and a Stage Model of Persuasion to Evaluate a Safety Message for Firefighters

A field study was conducted to evaluate the effectiveness of a National Institute for Occupational Safety and Health (NIOSH) health and safety message targeted at firefighters and to examine predictors of safety intentions among this group. This project examined: (a) the ability of the theory of planned behavior (TPB) to predict behavioral intentions for firefighters receiving a NIOSH occupational safety and health message; and (b) the use of a persuasion output matrix to assess message impact. A message about firefighting safety was nationally distributed to 36,000 fire chiefs, from which 781 were randomly selected to complete a survey assessing message impact and behavioral intentions. Results indicate message impact was weakest at the exposure, recall, and action stages of persuasion output. The TPB variables were found to significantly predict safety intentions

Formative Field Experiments of a NIOSH Alert to Reduce the Risks to Firefighters From Structural Collapse: Applying the Cascade Framework

The authors report two field experiments aimed at testing the impact of government safety recommendations. Using a cascade framework from the Communication Matrix (McGuire, 1985, 1989), the study tested effects of reminder cards, message format, argument quality, and mailer types on indicators of reception, processing, and response. Systematic combinations of these variables were mailed to randomly selected firefighting units in the United States. Fire chiefs were contacted by phone to complete a survey within the next month (Experiment 1, N = 2,000, 44% completion; Experiment 2, N = 600; 77% completion). Results showed highest reception rates (∼50%) with one reminder card and the standard government low-graphics format and that greater reception produced stronger intentions. Processing was stronger with the standard government low-graphics format, and processing was correlated with more positive attitudes and intentions. Response indexes were favorable (\u3e4 on -point scale) under all conditions. Outcomes are interpreted within the framework of a communication cascade model

A Communication Matrix Intervention to Increase Adoption of Federal Government Safety Recommendations

A 3-year, multichannel intervention project assessed adoption of federal government workplace safety testing methods among 3 randomly drawn samples of industrial hygienists. A communication matrix (McGuire, 1985, 1989) framework focusing on stages of reception, processing, and response was used to create, implement, and evaluate the intervention. Participants were interviewed by phone during 3 waves: baseline, immediately following year 1 of the intervention, and immediately following year 2 of the intervention. Results indicate a gain in reception over the course of the intervention. Increases in attitudes, control beliefs, intentions, and self-reported behavior were found between baseline and the 1st year of the intervention, and were maintained (although not increased) during the 2nd year of the intervention. Strengths and weaknesses of the intervention are viewed through the scope of the communication matrix

The Cost-Effectiveness of 1% Or Less Media Campaigns Promoting Low-Fat Milk Consumption

Introduction The purpose of our study was to compare the cost-effectiveness of four strategies using components of 1% Or Less to promote population-based behavior change. 1% Or Less is a mass-media campaign that encourages switching from high-fat (whole or 2%) to low-fat (1% or skim) milk. Using a quasi-experimental design, campaigns were previously conducted in four West Virginia communities using different combinations of 1) paid advertising, 2) media relations, and 3) community-based educational activities. Telephone surveys and supermarket milk sales data were used to measure the campaigns’ effectiveness. Methods Using data from the previously completed studies, we analyzed the cost of each campaign. We then calculated the cost per person exposed to the campaign and cost per person who switched from high- to low-fat milk. Results The combination of paid advertising and media relations was the most cost-effective campaign, with a cost of $0.57 per person to elicit a switch from high- to low-fat milk, and the combination of media relations and community-based educational activities was the least cost-effective campaign, with a cost of$11.85 per person to elicit a switch. Conclusion Population-based campaigns using a combination of paid advertising and media relations strategies can be a cost-effective way to promote a behavior change in a community