Connections Between the Spring Breakup of the Southern Hemisphere Polar Vortex, Stationary Waves, and Air-sea Roughness

A robust connection between the drag on surface-layer winds and the stratospheric circulation is demonstrated in NASA's Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). Specifically, an updated parameterization of roughness at the air-sea interface, in which surface roughness is increased for moderate wind speeds (4ms to 20ms), leads to a decrease in model biases in Southern Hemispheric ozone, polar cap temperature, stationary wave heat flux, and springtime vortex breakup. A dynamical mechanism is proposed whereby increased surface roughness leads to improved stationary waves. Increased surface roughness leads to anomalous eddy momentum flux convergence primarily in the Indian Ocean sector (where eddies are strongest climatologically) in September and October. The localization of the eddy momentum flux convergence anomaly in the Indian Ocean sector leads to a zonally asymmetric reduction in zonal wind and, by geostrophy, to a wavenumber-1 stationary wave pattern. This tropospheric stationary wave pattern leads to enhanced upwards wave activity entering the stratosphere. The net effect is an improved Southern Hemisphere vortex: the vortex breaks up earlier in spring (i.e., the spring late-breakup bias is partially ameliorated) yet is no weaker in mid-winter. More than half of the stratospheric biases appear to be related to the surface wind speed biases. As many other chemistry climate models use a similar scheme for their surface layer momentum exchange and have similar biases in the stratosphere, we expect that results from GEOSCCM may be relevant for other climate models

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