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

Isotope climatic record from ice core Dome C

Simple glaciological conditions at Dome C in east Antarctica have made possible a more detailed and accurate interpretation of an ice core to 950 m depth spanning some 32,000 yr than that obtained from earlier ice cores. Dated events in comparable marine core has enabled the reduction of accumulation rate during the last ice age to be estimated. Climatic events recorded in the ice core indicate that the warmest Holocene period in the Southern Hemisphere occurred at an earlier date than in the Northern Hemisphere

Influence of PC superplasticizers on tricalcium silicate hydration.

International audienceThe influence of polycarboxylate superplasticizers with variations of content of anionic groups was studied on pure tricalcium silicate hydration. The hydration in diluted suspension has been investigated by conductimetry, calorimetry, and ionic and total organic carbon analysis of the liquid phase. The tricalcium silicate hydration is always delayed in presence of polycarboxylate superplasticizer. Moreover, the delay can be correlated with the number of carboxylate groups which are on the adsorbed superplasticizer molecules. This effect seems to be due to a decrease of the C3S dissolution rate. Namely the pure C3S dissolution was studied by ICP with or without a carboxylate functionalized latex. A drastic decrease of the C3S dissolution rate was observed in presence of the polycarboxylate functionalized latex and this effect increased with higher hydroxyde calcium concentrations

Cloning, sequencing and functional expression of zebra (Equus burchelli) LH

International audienc