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

Surface treatments of CuGaSe2 by means of In,Ga S

CuGaSe2 CGSe thin films grown by close spaced chemical vapour transport CCSVT for photovoltaic applications have been subjected to dry chemical treatments with In, Ga, and S aiming at the modification of the near surface region of this compound. The goal is to find a feasible approach in order to overcome the limitations related to CGSe buffer formation and performance in complete devices. The incorporation of In and S into the near surface region of CGSe has proven to have a positive impact on device performance using CdS as buffer layer. In this contribution the main effects of In S CVD treatments on CCSVT grown CGSe thin films are reviewed, with special attention to metastability issues. Preliminary results on the extension of such treatments to Ga S will be presente

Direct measurement of Urbach tail and gap state absorption in CuGaSe2 thin films by photothermal deflection spectroscopy and the constant photocurrent method

The applicability of photothermal deflection spectroscopy PDS and the constant photocurrent method CPM to chemical vapor deposited CVD and physical vapor deposited PVD CuGaSe2 CGSe thin films is investigated. Process dependent variations in direct band gap energies, Urbach tail widths, bulk and surface defect densities of the films are given as a function of composition. Differences in the PDS and CPM absorption spectra of more than one order of magnitude are found. Using the standard a Si theory of PDS and CPM analysis, a two layer system consisting of a defect rich near surface layer and a less defective bulk layer is found in device quality films. Optical improvements due to the Ga Se annealing step as a second stage of the growth process result in a reduced bulk defect density while the near surface defect density remains unchange