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

Farmer’s knowledge, attitude and practice on rodent management in lowland irrigated rice in Central-eastern Tanzania

Journal of Plant Science.Rodents are one of the major factors limiting crop production in Central-eastern Tanzania. A quantitative study was conducted at Hembeti village to obtain information on knowledge, attitude and practice of villagers with respect to rodent management. Structured questionnaires were administered to 30 randomly selected farmers and the results obtained were analysed by the SPSS Ver. 12 Computer programme. It was revealed that 80-90% of the farmers cultivate maize and paddy in small fields ranging from 0.5 to 1.5 acres. Rodents were reported to be the leading pests causing 20- 60% crop losses both in fields and stores yearly. Methods used to assess presence of rodents in the area included presence of burrows and unearthed seedlings in fields and damaged grains and rodent noises in stores. It was further found out that farmers were responsible for control of rodents and that 53% and 47 % were using rodenticides and physical killing methods respectively. Financial constraints were reported to be the major factors limiting farmers to acquire and apply rodenticides. Need for training farmers on other management methods basing on ecological approaches was recommended

Food preferences of the multi-mammate mouse, Mastomys natalensis, in irrigated rice habitats in Tanzania

We investigated the composition of the diet of the multi-mammate mouse, Mastomys natalensis, within irrigated rice and fallow field habitats at set time periods related to rice crop growth stages. In both habitats, vegetative plant material, i.e. leaves, stems and seeds, were the most abundant components of the rodent’s diet, while other food types (invertebrates, fruits) were observed only in low quantities. We conclude that vegetative plant material and seeds were the main types of food consumed not only due to their relatively higher abundance in the environments under study but also because of the highly specialised herbivorous/granivorous nature of the dominant rodent species, M. natalensis. Thus, the introduction and expansion of continuous rice-cropping using irrigation in Tanzania is likely to be severely constrained by the presence of M. natalensis. In our opinion, field hygiene, including the removal of alternative food resources and nesting sites for M. natalensis near cropping areas, may help to both lower rodent population numbers and reduce immigration potential. Nonchemical rodent control methods such as trap barrier systems developed for lowland irrigated rice in south-eastern Asia should, we argue, be evaluated for their effectiveness under African conditions

Grazing-associated infochemicals induce colony formation in the green alga Scenedesmus

In this study we demonstrate a new form of immunoregulation: engagement on CD4(+) T cells of the complement regulator CD46 promoted the effector potential of T helper type 1 cells (T(H)1 cells), but as interleukin 2 (IL-2) accumulated, it switched cells toward a regulatory phenotype, attenuating IL-2 production via the transcriptional regulator ICER/CREM and upregulating IL-10 after interaction of the CD46 tail with the serine-threonine kinase SPAK. Activated CD4(+) T cells produced CD46 ligands, and blocking CD46 inhibited IL-10 production. Furthermore, CD4(+) T cells in rheumatoid arthritis failed to switch, consequently producing excessive interferon-γ (IFN-γ). Finally, γδ T cells, which rarely produce IL-10, expressed an alternative CD46 isoform and were unable to switch. Nonetheless, coengagement of T cell antigen receptor (TCR) γδ and CD46 suppressed effector cytokine production, establishing that CD46 uses distinct mechanisms to regulate different T cell subsets during an immune response