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

The influence of nutrition on production of container-growth ornamental peppers

Three experiments were conducted to study the influence of nutrition on the production of container-grown Capsicum annuum 'Fips': the first was a central composite design which examined the influence of five rates of N, P, K and lime: 0 to 600 g N m⁻³, 0 to 400 g P m⁻³ , 0 to 332 g K m⁻³ and 0 to 12 kg lime m⁻³. The second experiment was a 4 X 2 X 2 factorial with 4 rates of Mg from 0 to 450 gm⁻³ , 2 rates of P at 50 and 400 gm⁻³ and 2 rates of K at 83 and 415 gm⁻³. The third experiment was a simple randomised block design with 5 rates of K from 300 to 700 gm⁻³ Strong responses to N and K were noted while P had a moderate influence. Lime had no apparent effect at low N rates but influenced growth significantly at high N by raising the pH from 4.2 to 5.8. There was no response to added Mg. Foliage growth, plant quality and fruiting were optimal at 600 g N, 300 g P and 500 g K m⁻³. Lime at 6 kg m⁻³ was recommended (optimum pH 5.8 - 6.1). Suggested tissue composition of good quality ornamental pepper 'Fips' are given as 3.4 to 3.8% N, 0.4% P, 4.6% K, 3.4% Ca, and 1.4% Mg

Effects of nitrogen, phosphorus, potassium, and B-Nine on the growth of Brompton stocks (Matthiola incana)

The effects of five levels of nitrogen (N), phosphorus (P), and potassium (K) and B-Nine (B9) on Brompton stocks (Matthiola incana) grown in peat/sand 1:1 (V.V.) were studied. Nitrogen strongly promoted growth which was further enhanced by high K. Deficiency symptoms occurred at low K whereas there was little demand for P, and it tended to depress the response to N. A foliar spray of B9 strongly reduced height and was temporarily phytotoxic at 5000 and 6000 ppm. The two concentrations offset the response to N particularly at 450 and 600g N/m3 where there was a mild N X B9 negative interaction for foliar dry weight

Certain factors affecting the production of container-grown ornamental peppers (Capsicum annuum L.)

The objectives of this study were to examine three aspects of the production of Capsicum spp. grown as ornamental peppers: 1. Nutritional trials are set up to examine the influence of N, P, K, Ca and Mg on growth and quality of container-grown ornamental peppers and to determine suitable nutrient levels for a potting mix to be used for the production of these peppers. 2. Shade experiments are conducted to study the influence of light levels on the production of container-grown ornamental peppers and to recommend, if appropriate, a specific production light level for optimum growth and plant quality. 3. Experiments with growth regulators are intended to investigate the value of foliar sprays of B9, CCC and Ethrel as a substitute for hand-pinching to produce compact and high quality ornamental peppers. Recommendations could then be made on suitable spray concentrations for each of these growth regulators