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

On lower bound antenna efficiency measurements in a reverberation chamber

Abstract—This paper addresses a few specific aspects of mea-suring the lower bound of antenna efficiency in a reverberation chamber. While the initial method for measuring the lower bound of efficiency has been presented, three key revisions are discussed here: (1) an updated notation, (2) a revised method for calculating the lower bound of efficiency, and (3) a new method for combining stirring techniques. The updated antenna model notation is designed to be more general and applicable to situations with n antennas. The revised efficiency calculation targets an issue of the original method where the minimum bounding circle exceeded the unit circle. Introducing a new method of combining stirring techniques addresses a weakness of the original model. For the model to work well, it needs a very large number of paddle positions that generate a good statistical approximation of the environment (in this case, a reverberation chamber). As a possible remedy to this weakness, we propose a different way of combining stirring techniques. I

A novel method for determining the lower bound of antenna efficiency

Determining absolute transmitting efficiency has been a difficult task since the inception of the antenna itself. While methods that can measure transmitting efficiency do exist, most are complicated and prone to high uncertainties. A new method is presented for determining the lower bound of absolute transmitting efficiency by use of a reverberation chamber. This method is able to characterize both the transmitting and receiving efficiency of an antenna. After the method is derived, numerical simulations are presented. These simulations can provide insight into the behavior of the equations and necessary assumptions. Then, by use of measurement data, the method for transmitting efficiency is compared to efficiency data obtained from another reverberation chamber method. Data for this comparison will come from two different types of antennas: a wide band dual-ridged horn, and a narrow-band meta-material inspired antenna. Following the measurement data, possible areas for improvement of the method and its optimization are discussed

Spectrum sensing with WLAN access points

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Demultiplexing spectrum-sharing field sources with distributed field probes

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Testing spectrum sensing networks by UAV

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