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 New Flexible Sigmoidal Growth Model

Biological growth is driven by numerous functions, such as hormones and mineral nutrients, and is also involved in various ecological processes. Therefore, it is necessary to accurately capture the growth trajectory of various species in ecosystems. A new sigmoidal growth (NSG) model is presented here for describing the growth of animals and plants when the assumption is that the growth rate curve is asymmetric. The NSG model was compared with four classic sigmoidal growth models, including the logistic equation, Richards, Gompertz, and ontogenetic growth models. Results indicated that all models fit well with the empirical growth data of 12 species, except the ontogenetic growth model, which only captures the growth of animals. The estimated maximum asymptotic biomass w m a x of plants from the ontogenetic growth model was not reliable. The experiment result shows that the NSG model can more precisely estimate the value and time of reaching maximum biomass when growth rate becomes close to zero near the end of growth. The NSG model contains three other parameters besides the value and time of reaching maximum biomass, and thereby, it can be difficult to assign initial values for parameterization using local optimization methods (e.g., using Gauss&#8315;Newton or Levenberg&#8315;Marquardt methods). We demonstrate the use of a differential evolution algorithm for resolving this issue efficiently. As such, the NSG model can be applied to describing the growth patterns of a variety of species and estimating the value and time of achieving maximum biomass simultaneously

Have market-oriented reforms decoupled China's CO₂ emissions from total electricity generation? An empirical analysis

Achieving the decoupling of electric CO2 emissions from total electricity generation is important in ensuring the sustainable socioeconomic development of China. To realize this, China implemented market-oriented reforms to its electric power industry at the beginning of 2003. This study used the Tapio decoupling index, the Laspeyres decomposition algorithm, and decoupling-related data from 1993 to 2012 to evaluate the effect of these reforms. Several conclusions can be drawn based on the empirical analysis. (1) The reforms changed the developmental trend of the decoupling index and facilitated its progress towards strong decoupling. (2) The results forecasted through fitting the curve to the decoupling index indicate that strong decoupling would be realized by 2030. (3) Limiting the manufacturing development and upgrading the generation equipment of the thermal power plants are essential for China to achieve strong decoupling at an early date. (4) China should enhance regulatory pressures and guidance for appropriate investment in thermal power plants to ensure the stable development of the decoupling index. (5) Transactions between multiple participants and electricity price bidding play active roles in the stable development of the decoupling index