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

Orthorhombic superstructures within the rare earth strontium-doped cobaltate perovskites: Ln 1- x Sr x CoO 3-δ ( Ln = Y 3+ , Dy 3+ -Yb 3+ ; 0.750≤ x ≤0.875)

A combination of electron, synchrotron X-ray and neutron powder diffraction reveals a new orthorhombic structure type within the Sr-doped rare earth perovskite cobaltates Ln1-xSrxCoO3-δ (Ln=Y3+, Dy3+, Ho3+, Er3+, Tm3+and Yb3+). Electron diffraction show

Comet-like tail-formation of exospheres of hot rocky exoplanets: Possible implications for CoRoT-7b

International audienceIn this study, the interaction of stellar wind plasma with the exosphere and possibly with the planetary magnetospheric environment of close-in rocky exoplanets is investigated. In particular, we focus on the "super-Earth" CoRoT-7b, which has been recently discovered by the CoRoT space observatory. The physical properties of such a planet, with an orbital distance of about 0.017 AU from its host star, may most likely resemble a big and more massive Mercury-type planet in the sense that it most likely releases its surface elements into space. Based on the present knowledge of CoRoT-7b and drawing on the analogy to Solar System planets, we use numerical models to simulate exospheric and magnetospheric distributions of different particle populations, among which are neutral sodium and ionised calcium and magnesium. We find that, for most species, the atmospheric loss rate in such an extreme environment can be very high, so that a neutral and an ionised tail of escaping particles will form. Depending on the planetary composition we postulate the presence of a sodium tail, similar to that of Mercury but shorter due to the shorter Na lifetime, and of an extended magnetospheric distribution of ionised calcium or magnesium. The feasibility of observation of such populations is also discussed

Conservation of the Ethiopian church forests: Threats, opportunities and implications for their management

In the central and northern highlands of Ethiopia, native forest and forest biodiversity is almost confined to sacred groves associated with churches. Local communities rely on these 'church forests' for essential ecosystem services including shade and fresh water but little is known about their region-wide distribution and conservation value. We (1) performed the first large-scale spatially-explicit assessment of church forests, combining remote-sensing and field data, to assess the number of forests, their size, shape, isolation and woody plant species composition, (2) determined their plant communities and related these to environmental variables and potential natural vegetation, (3) identified the main challenges to biodiversity conservation in view of plant population dynamics and anthropogenic disturbances, and (4) present guidelines for management and policy. The 394 forests identified in satellite images were on average ~2ha in size and generally separated by ~2km from the nearest neighboring forest. Shape complexity, not size, decreased from the northern to the central highlands. Overall, 148 indigenous tree, shrub and liana species were recorded across the 78 surveyed forests. Patch α-diversity increased with mean annual precipitation, but typically only 25 woody species occurred per patch. The combined results showed that >50% of tree species present in tropical northeast Africa were still present in the 78 studied church forests, even though individual forests were small and relatively species-poor. Tree species composition of church forests varied with elevation and precipitation, and resembled the potential natural vegetation. With a wide distribution over the landscape, these church forests have high conservation value. However, long-term conservation of biodiversity of individual patches and evolutionary potential of species may be threatened by isolation, small sizes of tree species populations and disturbance, especially when considering climate change. Forest management interventions are essential and should be supported by environmental education and other forms of public engagement.publisher: Elsevier articletitle: Conservation of the Ethiopian church forests: Threats, opportunities and implications for their management journaltitle: Science of The Total Environment articlelink: http://dx.doi.org/10.1016/j.scitotenv.2016.02.034 content_type: article copyright: Copyright © 2016 Elsevier B.V. All rights reserved.status: publishe