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

Effect of Nutrient Management Practices on Carbon Pools Following 13 Year of Cropping with Soybean (Glycine max) Based Cropping Systems in Vertisol of Central India

Organic manure application has its significant impact on the soil health. Low organic matter in tropical soils is a major factor contributing to their poor productivity. Soil properties have been continuously influenced by the management practices and land uses, in which latter one has been, identified as profound influence on soil properties especially on soil organic carbon. A thirteen year experiment on soybean based cropping system in a vertisol of central india under organic farming was used for this investigation An investigation was carried out on “Soil organic carbon dynamics under long-term nutrient management in soybean based cropping system” at the Indian Institute of Soil Science, Bhopal on an on-going research project on organic farming. The effect of organic, integrated and inorganic nutrient management was assessed in three cropping systems viz. soybean (JS 335)-wheat (Malwa Shakti), soybean-mustard (Pusa Bold) and soybean-gram (JG 130) on aggregate size fractions, carbon content in aggregate as well as soil organic carbon pools dynamics on a split plot experimental design with three replications. The study relevant to dynamics of soil organic carbon pools revealed higher content of soil organic carbon, labile carbon, water soluble carbon, SMBC as well as dehydrogenase activity that varied between 1.04 and 0.86 percent; 440 and 538 mg kg-1, 52.97 and 70.43; 288 and 375 mg kg-1, 88 and 137 µg TPF g-1 soil d-1, respectively in surface 0-15 cm soil under organic nutrient management