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

A comparative study on the efficiency of leaf infusions from selected native plants as oviposition attractants for Aedes aegypti L

Aedes aegypti mosquitoes are known vectors of epidemic diseases such as chikungunya, zika, and dengue. The vaccine against the dengue virus, a confirmed viral infection in the country by the Department of Health, is still under investigation. Data on the vaccine efficacy are insufficient, which is why other means of controlling the disease is being explored. Active monitoring and surveillance of vectors should be done to determine the effectiveness of other control interventions. The research was conducted to perform a comparative analysis of different oviposition attractants, mainly leaf infusions, for Ae. aegypti mosquitoes. This research also examined which time of the day the mosquitoes prefer to oviposit. Two tests were done: oviposition attractant evaluation using No Choice and Choice tests, and time of oviposition preference through Oviclock chamber. For evaluation of oviposition attractant, treatments included are infusions from lawanit, hay, bamboo, and a new tea bag infusion, water served as the control check. In the No Choice test, five gravid female mosquitoes were placed in each cage with specific leaf infusions while in the Choice test, 25 gravid female mosquitoes were placed in cages with all the infusions arranged randomly. Both experiments were replicated three times. The mosquitoes were allowed to oviposit for three days. Both tests revealed that hay infusion had significantly the highest number of eggs laid. In the Oviclock experiment, hay infusion was used as the oviposition attractant being the most preferred attractant based on the oviposition attractant experiment. The experiment was performed for a total of 24 hours. Results showed that Ae. aegypti preferred to lay eggs between 1700H to 2200H, with 1900H being the peak hour of oviposition, which revealed oviposition time mostly in the evening similar to previous works. Result of these experiments is essential in the design of a trapping system for Ae. aegypti, which needs further exploration

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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