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

Factors Affecting Incidence of Sclerotinia Stem Rot of Rapeseed (Canola)

In a study of sclerotinia stem rot in commercial rapeseed fields in East and West Central Saskatchewan in 1983 and 1984, several factors relating to inoculum density were monitored when the crops were in bloom. Carpogenically-germinated sclerotia were counted in I II specific areas. The frequencies of Sclerotinia-infested live and dead petals, leafaxils and leaf bases were determined by plating on potato dextrose agar with added rose bengal and streptomycin. The final percentage of diseased plants was determined shortly before the crops were swathed. The results demonstrated a significant relationship between petal infestation at early bloom and final disease. Significant relationships between germinated sclerotia and disease were obtained only with intensive sampling. Infested petals and disease were regularly found when apothecia were absent, thereby demonstrating the infective potential of extrinsically produced ascospores. The possibility of using petal infestation to forecast stem rot and improve the economics of chemical control is discussed; however, several, refinements in the technique are required. Laboratory studies demonstrated the potential for petals to be colonized by. sclerotiorum before falling from the inflorescences onto plant surfaces. Laboratory and field studies of the persistence of water droplets in leaf axils, a major infection court of rapeseed, demonstrated that water sometimes persisted for relatively long periods even when ambient environmental conditions were generally unfavorable for infection. In view of the moisture requirements for infection, this may partially explain the occurrence of low to moderate levels of disease in some rapeseed fields during relatively dry years

SES0787LS camelina

SES0787LS is a camelina (Camelina sativa) cultivar developed at Smart Earth Camelina Corporation in Saskatoon, Saskatchewan. It was developed via hybridization followed by pedigree selection. SES0787LS has significantly higher (12%) seed yield and significantly larger seeds (29.6%) than the check cultivar AAC 10CS0048 and is adapted to all soil zones of the Canadian Prairies.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Single-nucleotide polymorphism identification and genotyping in Camelina sativa

Camelina sativa, a largely relict crop, has recently returned to interest due to its potential as an industrial oilseed. Molecular markers are key tools that will allow C. sativa to benefit from modern breeding approaches. Two complementary methodologies, capture of 3\u2032 cDNA tags and genomic reduced-representation libraries, both of which exploited second generation sequencing platforms, were used to develop a low density (768) Illumina GoldenGate single nucleotide polymorphism (SNP) array. The array allowed 533 SNP loci to be genetically mapped in a recombinant inbred population of C. sativa. Alignment of the SNP loci to the C. sativa genome identified the underlying sequenced regions that would delimit potential candidate genes in any mapping project. In addition, the SNP array was used to assess genetic variation among a collection of 175 accessions of C. sativa, identifying two sub-populations, yet low overall gene diversity. The SNP loci will provide useful tools for future crop improvement of C. sativa.Peer reviewed: YesNRC publication: Ye