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

Modeling and Simulation of Compressible Three-Phase Flows in an Oil Reservoir: Case Study of Tsimiroro Madagascar

International audienceOil extraction represents an important investment and the control of a rational exploitation of a field means mastering various scientific techniques including the understanding of the dynamics of fluids in place. This paper presents a theoretical investigation of the dynamic behavior of an oil reservoir during its exploitation. More exactly, the mining process consists in introducing a miscible gas into the oil phase of the field by means of four injection wells which are placed on four corners of the reservoir while the production well is situated in the middle of this one. So, a mathematical model of multiphase multi-component flows in porous media was presented and the cell-centered finite volume method was used as discretization scheme of the considered model equations. For the simulation on Matlab, the case of the oilfield of Tsimiroro Madagascar was studied. It ensues from the analysis of the contour representation of respective saturations of oil, gas and water phases that the conservation law of pore volume is well respected. Besides, the more one moves away from the injection wells towards the production well; the lower is the pressure value. However, an increase of this model variable value was noticed during production period. Furthermore, a significant accumulated flow of oil was observed at the level of the production well, whereas the aqueous and gaseous phases are there present in weak accumulated flow. The considered model so allows the prediction of the dynamic behavior of the studied reservoir and highlights the achievement of the exploitation process aim

A stereoscopic study of the mouthparts of the marine isopod, Cirolana bovina (Isopoda: Flabellifera)

The three-dimensional study of the mouthparts of the isopod crustacean Cirolana bovina is carried out for specimens collected from the Mediterranean Sea, Alexandria, Egypt, to reveal their morphology and related cuticular microstructures, especially setal types. The mouthparts consist of a labrum, paragnaths, paired mandibles, maxillules, maxillae and maxillipeds. The labrum and the paragnaths are the least developed but peculiarly the mandibles are asymmetrical, large, stout and highly modified. The possible functions of the mouthparts, especially in feeding are discussed in light of their structure. KEY WORDS: Crustacea, isopods, SEM, mouthparts, cuticular microstructures. Egyptian Journal of Biology Vol.3(2) 2001: 20-2