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

Dissecting the Polygenic Basis of Cold Adaptation Using Genome-Wide Association of Traits and Environmental Data in Douglas-fir

Understanding the genomic and environmental basis of cold adaptation is key to understand how plants survive and adapt to different environmental conditions across their natural range. Univariate and multivariate genome-wide association (GWAS) and genotype-environment association (GEA) analyses were used to test associations among genome-wide SNPs obtained from whole-genome resequencing, measures of growth, phenology, emergence, cold hardiness, and range-wide environmental variation in coastal Douglas-fir (Pseudotsuga menziesii). Results suggest a complex genomic architecture of cold adaptation, in which traits are either highly polygenic or controlled by both large and small effect genes. Newly discovered associations for cold adaptation in Douglas-fir included 130 genes involved in many important biological functions such as primary and secondary metabolism, growth and reproductive development, transcription regulation, stress and signaling, and DNA processes. These genes were related to growth, phenology and cold hardiness and strongly depend on variation in environmental variables such degree days below 0c, precipitation, elevation and distance from the coast. This study is a step forward in our understanding of the complex interconnection between environment and genomics and their role in cold-associated trait variation in boreal tree species, providing a baseline for the species&rsquo; predictions under climate change

Dissecting the Polygenic Basis of Cold Adaptation Using Genome-Wide Association of Traits and Environmental Data in Douglas-fir

Understanding the genomic and environmental basis of cold adaptation is key to understand how plants survive and adapt to different environmental conditions across their natural range. Univariate and multivariate genome-wide association (GWAS) and genotype-environment association (GEA) analyses were used to test associations among genome-wide SNPs obtained from whole-genome resequencing, measures of growth, phenology, emergence, cold hardiness, and range-wide environmental variation in coastal Douglas-fir (Pseudotsuga menziesii). Results suggest a complex genomic architecture of cold adaptation, in which traits are either highly polygenic or controlled by both large and small effect genes. Newly discovered associations for cold adaptation in Douglas-fir included 130 genes involved in many important biological functions such as primary and secondary metabolism, growth and reproductive development, transcription regulation, stress and signaling, and DNA processes. These genes were related to growth, phenology and cold hardiness and strongly depend on variation in environmental variables such degree days below 0c, precipitation, elevation and distance from the coast. This study is a step forward in our understanding of the complex interconnection between environment and genomics and their role in cold-associated trait variation in boreal tree species, providing a baseline for the species’ predictions under climate change

Dissecting the Polygenic Basis of Cold Adaptation Using Genome-Wide Association of Traits and Environmental Data in Douglas-fir

Understanding the genomic and environmental basis of cold adaptation is key to understand how plants survive and adapt to different environmental conditions across their natural range. Univariate and multivariate genome-wide association (GWAS) and genotype-environment association (GEA) analyses were used to test associations among genome-wide SNPs obtained from whole-genome resequencing, measures of growth, phenology, emergence, cold hardiness, and range-wide environmental variation in coastal Douglas-fir (Pseudotsuga menziesii). Results suggest a complex genomic architecture of cold adaptation, in which traits are either highly polygenic or controlled by both large and small effect genes. Newly discovered associations for cold adaptation in Douglas-fir included 130 genes involved in many important biological functions such as primary and secondary metabolism, growth and reproductive development, transcription regulation, stress and signaling, and DNA processes. These genes were related to growth, phenology and cold hardiness and strongly depend on variation in environmental variables such degree days below 0c, precipitation, elevation and distance from the coast. This study is a step forward in our understanding of the complex interconnection between environment and genomics and their role in cold-associated trait variation in boreal tree species, providing a baseline for the species' predictions under climate change

Impact 2003

Index Competitive Agricultural Systems in a Global Economy Biosecurity Education .................................................. 1 Calf Scours Prevention System .................................................. 2 Center for Agricultural & Food Industrial Organization .................................................. 3 Chickpeas as an Alternative Crop .................................................. 5 .................................................. 6 Dry Ethanol Byproducts for Farms and Ranches .................................................. 7 Indoor Prawn Production .................................................. 8 National Drought Mitigation Center .................................................. 9 Republican River Basin Irrigation Management Project .................................................. 11 Small Farm and Ranch Profitability Project .................................................. 12 Sorting and Mixing Pigs .................................................. 14 WeedSOFT Aids Weed Management Decisions ....................................15 New Beef Products Add Value* ....................................16 Panhandle Chicory Production* ....................................18 Ranch Practicum* .................................... 19 Turf Grass Seed Production* .................................... 20 Safe and Secure Food and Fiber Systems Biosecurity Education ................................................ 21 E. coli Research .................................... 22 Testing Oil Freshness .................................... 24 Healthy, Well-Nourished Population Food Safety and Nutrition Web Site ....................................25 Improving Young Adults\u27 Eating Habits ....................................26 Nutrition Education Programs* ....................................27 Smoking and Diet* .................................... 28 Sun-Protective Clothing Standards* ....................................29 Greater Harmony Between Agriculture and the Environment Buffer Strip Assessment Tool .................................... 30 Irrigation Management Home Study Course .......................................................................................... 31 Livestock and Poultry Environmental Stewardship Curriculum ........................................................ 32 Monitoring Lake Water Quality ....................................33 Nitrogen Management in Crop Production ............................................................................................. 34 Republican River Basin Irrigation Management Project ....................................35 Rootworm Resistance Research ....................................36 WeedSOFT Aids Weed Management Decisions ....................................37 Cleaning Up Pesticide-Contaminated Soil* ....................................38 Measuring Carbon Storage in Cropland* ....................................40 Pivots, Nitrogen Management Protect Water Quality* .............................................. 41 Reducing Livestock Methane* ....................................42 Economic Development and Quality of Life for People and Communities Bridging the Technology Gap ....................................43 Consumer Preference and Economic Leakage Study Program ....................................44 Decorative Millet Earns All-America Selections. Gold ....................................45 Distance Counseling Improves Access for Rural Residents ................................................................. 46 Drought Web Site .................................... 47 Forensic Entomology .................................... 48 National Drought Mitigation Center ....................................49 Nebraska Rural Poll Provides Rural Perspective ....................................51 Protecting Water Quality Along the Lower Platte River ........................................................................ 53 Rural Women\u27s Concerns .................................... 54 Small Farm and Ranch Profitability Project ............................................................................................. 55 Technical Assistance for Geothermal Systems ........................................................................................ 57 Building Nebraska Families* .................................... 58 Coping with Divorce* .................................... 59 Food Processing Center Entrepreneurship Services* ............................................................................. 60 Giving Entrepreneurs an EDGE* ....................................61 Meat Plants Changing Rural Communities* ....................................62 New Beef Products Add Value* ................................................. 63 Panhandle Chicory Production* ....................................65 Sandhills Leadership Program* ................................................ 66 Technologies Across Nebraska* ....................................67 Society-Ready Graduates Animal Welfare Class ..................................................................... 68 Employment Seminar ............................................................. 69 Entomology Distance Education Master\u27s Degree ........................................... 70 Feedlot Management Specialization Internship ............................ 71 Food Product Development Class ................................................ 72 Innovative Uses for Soybeans ........................................................ 73 Pollution Prevention Internship .................................................................. 74 Student Development Initiative ..................................................... 76 Agricultural Science Magnet Schools*............................................... 77 America\u27s Farm* ...................................................................... 78 Bug Bash* .................................................................................. 79 Nebraska Beef Team* ........................................................ 8