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 pass-through of monetary rates to bank interest rates: implications for monetary policy

I study the pass-through of monetary rates into bank interest rates using both empirical and theoretical methods. I use the results of my study to derive implications for the conduct of monetary policy. Chapter 1, co-authored with Cynthia Balloch, provides theory and evidence that banks’ profitability and credit supply fundamentally depend on the level of nominal interest rates. I use a forty-year panel of Japanese banks to show that their profitability and lending terms depend on the level of nominal interest rates. These facts hold in the aggregate and in the cross-section, where I exploit bank heterogeneity. I build a macroeconomic model that rationalizes these facts and use it to study the implications for the aggregate supply of credit and the choice of an optimal inflation target. Chapter 2 , co-authored with Markus Brunnermeier, studies how bank lending reacts to monetary policy shocks in very-low or negative interest rate environments. In such environments, further decrease in rates can lead to lower bank profitability if banks are not sufficiently hedged, generating lower credit supply when their credit constraints bind. When these effects dominate the stimulatory effects of monetary shocks coming from presence of sticky prices, monetary policy reaches a “reversal rate” below which interest rate cuts are contractionary for lending. Chapter 3 studies how banks pass-through changes in monetary rates into their bank product. I study both bank assets, such as loans, and bank liabilities, such as various forms of deposits. I show that there is significant heterogeneity across products, and that the pass-through is highly non-linear, with dependence on the direction of the change as well as the economy’s state. The heterogeneity in bank product pass-through delivers heterogeneous pass-through to households that positively correlate with their liquid wealth. I show in a heterogenous-agents New Keynesian model that this reduces monetary policy propagation, affects the Taylor principle, and makes any effective lower bound – such as the reversal rate – bind more often

EXCESS workshop: Descriptions of rising low-energy spectra

International audienceMany low-threshold experiments observe sharply rising event rates of yet unknown origins below a few hundred eV, and larger than expected from known backgrounds. Due to the significant impact of this excess on the dark matter or neutrino sensitivity of these experiments, a collective effort has been started to share the knowledge about the individual observations. For this, the EXCESS Workshop was initiated. In its first iteration in June 2021, ten rare event search collaborations contributed to this initiative via talks and discussions. The contributing collaborations were CONNIE, CRESST, DAMIC, EDELWEISS, MINER, NEWS-G, NUCLEUS, RICOCHET, SENSEI and SuperCDMS. They presented data about their observed energy spectra and known backgrounds together with details about the respective measurements. In this paper, we summarize the presented information and give a comprehensive overview of the similarities and differences between the distinct measurements. The provided data is furthermore publicly available on the workshop’s data repository together with a plotting tool for visualization