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

Mechanical and Thermal Properties of Synthetic Polypropylene Fiber–Reinforced Renewable Oil Palm Shell Lightweight Concrete

Oil palm shell (OPS) is an agricultural solid waste from the extraction process of palm oil. All these wastes from industry pose serious disposal issues for the environment. This research aims to promote the replacement of conventional coarse aggregates with eco-friendly OPS aggregate which offers several advantages, such as being lightweight, renewable, and domestically available. This paper evaluates the mechanical and thermal performances of renewable OPS lightweight concrete (LWC) reinforced with various type of synthetic polypropylene (SPP) fibers. Monofilament polypropylene (MPS) and barchip polypropylene straight (BPS) were added to concrete at different volume fractions (singly and hybrid) of 0%, 0.1%, 0.3% and 0.4%. All specimens were mixed by using a new mixing method with a time saving of up to 14.3% compared to conventional mixing methods. The effects of SPP fibers on the mechanical properties were investigated by compressive strength, splitting tensile strength and residual strength. The strength of the oil palm shell lightweight concrete hybrid 0.4% (OPSLWC–HYB–0.4%) mixture achieved the highest compressive strength of 29 MPa at 28 days. The inclusion of 0.3% of BPS showed a positive outcome with the lowest thermal conductivity value at 0.55 W/m °C. Therefore, the results revealed that incorporation of BPS fiber enhanced the performance of thermal conductivity tests as compared to inclusion of MPS fiber. Hence, renewable OPS LWC was proven to be a highly recommended environmentally friendly aggregate as an alternative solution to replace natural aggregates used in the concrete industry