ニホンノチャエンニオケルチッソヒリョウケイタイガアサンカチッソハッセイトドジョウオヨビチャバノトクセイニアタエルエイキョウ

博士（農学）東京農工大

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 Biochar and Irrigation on the Interrelationships among Soybean Growth, Root Nodulation, Plant P Uptake, and Soil Nutrients in a Sandy Field

To investigate the interrelationships among biochar, soil nutrients, and soybean plant growth in more detail, the root nodulation response of soybean (Glycine max L.) to biochar application was analyzed in a field study. We further examined the biochar effect on soil phosphatase activity to elucidate the relationships among biochar, phosphatase activity, and plant phosphorus uptake. Soybean was planted in a sandy field wherein the biochar and irrigation conditions were considered the two treatment factors. In our result, irrigation increased the pod number and plant height by 20.7% and 11.1%, respectively. Irrigation reduced the shoot and root dry matter content by 67.9% and 75.1%, respectively. The nodule number increased by 37% due to biochar addition under irrigated conditions. The soil carbon concentration was elevated by 13.4% with biochar application under rainfed conditions. Acid phosphomonoesterase (APM) was increased by 21.8% in the biochar-incorporated plots under the irrigated condition. Principal component analysis and redundancy analysis suggested that biochar application enhanced the relationships between the nodule number and soil potassium and magnesium concentrations. The correlation between soil sulfur content and nodule number was eliminated by biochar application. APM activity was associated with higher shoot and root phosphorus content and shoot dry weight after biochar application.Peer Reviewe

Nitrous Oxide Emission from Organic Fertilizer and Controlled Release Fertilizer in Tea Fields

A field experiment was conducted for two years in the Green Tea Laboratory of Saitama Prefectural Agriculture and Forestry Research Center, Iruma, Saitama, Japan from March 2014 to December 2015. Controlled release fertilizers (CRF) or organic fertilizers (ORG), which are a mixture of chicken manure and oil cake, were applied with the amount of 450 kg·N·ha−1·year−1 in 2014 and 397 kg·N·ha−1·year−1 in 2015. Nitrous oxide (N2O) emissions from soil in green tea fields were measured by the closed chamber method. The results showed that CRF has significantly lower N2O compared to ORG. The cumulative N2O emissions from CRF accounted for 51% of N2O emissions from ORG fields and 138% of control with no fertilizer treatment. The N2O flux from the row was higher than that under the canopy, since fertilizer was applied on the row. However, the total emission from the area between the rows was lower than that under the canopy because the area ratio between the row and canopy was 1:5.Peer Reviewe