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

Power output stabilizing feature in perovskite solar cells at operating condition: Selective contact-dependent charge recombination dynamics

WOS:000471201800016Stabilized power output at maximum power point (mpp) has been considered as one of the most reliable parameters as it provides a key performance indicator for perovskite solar cells (PSCs) revealing the operational stability of the photovoltaic device. Here, we show the effect of selective contact on the power output change under mpp tracking, which closely correlates with the charge recombination dynamics with a time scale of minutes. The normal n-i-p cell architecture comprising cp-TiO2/mp-TiO2/perovskite/spiro-MeOTAD (doped by either Li-TFSI or Zn-TFSI2) and the inverted p-i-n structure, NiOx/perovskite/PCBM, are examined to investigate the specific effect of the nature of the interface on operational stability. The normal structure with Li-TFSI shows a gradual performance decrease at mpp owing to the enhanced recombination at the interface between the perovskite and the spiro-MeOTAD, becoming the dominant recombination process, although the bulk-related recombination is suppressed. On the other hand, the inverted structure demonstrates an improved photocurrent at mpp due to the effectively suppressed recombination both in bulk and at the interface. Remarkably, the deteriorating performance of the normal structure with Li-TFSI at mpp is successfully avoided by replacing Li-TFSI with Zn-TFSI2, leading even to an increased power output with stable performance at mpp.European Union's Horizon 2020 research and innovation programme [785219]; King Abdulaziz City for Science and Technology; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2214]This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 785219. M.G., S.M.Z gratefully acknowledges King Abdulaziz City for Science and Technology for the financial support. S.A. would like to thank TUBITAK - 2214-A International Doctoral Research Fellowship Programme, for supporting his research at EPFL

High protein and mRNA expression levels of TUBB3 (class III beta-tubulin) are associated with aggressive tumor features in esophageal adenocarcinomas

Background: Esophageal adenocarcinomas show an increasing incidence in the Western world and their overall survival remains low. Microtubules are multifunctional cytoskeletal proteins involved in crucial cellular roles, including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Microtubulus-TUBB3 was found overexpressed in several carcinomas suggesting a significant role in cancer development. High levels of TUBB3 expression were also described to be associated with poor clinical outcome in various cancers. It was shown that overexpression of TUBB3 could be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types. Results: There is a statistically significant association between high TUBB3 protein and TUBB3 mRNA expression and shortened survival (p<0,0001). Prognostic impact of TUBB3 expression is seen in patients with and without multimodal treatment. Multivariate analysis revealed a strong TUBB3 expression to be an independent prognosis factor. Validation of protein expression by mRNA in situ hybridization underlines the credibility of the immunohistochemical results. Discussion: Our study emphasized the significant importance of TUBB3 in esophageal adenocarcinoma. TUBB3 serves as an independent prognostic marker and may be a valuable biomarker for routine application in esophageal adenocarcinoma especially to address the need for adjuvant treatment in individuals following neoadjuvant therapy and surgery. Future prospective studies are needed which include the results of TUBB3 in preoperative biopsy material to proof the prognostic impact of TUBB3. Materials and Methods: 280 esophageal adenocarcinomas that underwent primary surgical resection or resection after neoadjuvant therapy were analyzed by mRNA-in-situ-hybridization (RNAscope (R)) and by immunohistochemistry (TUBB3 rabbit monoclonal antibody; Epitomics)

Novel p-dopant toward highly efficient and stable perovskite solar cells

WOS:000448339100022Li-TFSI is the most common p-dopant for the hole conductor spiro-MeOTAD in the normal structure (n-i-p) of perovskite solar cells (PSCs), which consistently yield the highest power conversion efficiency (PCE) albeit at the risk of lower long-term operational stability. Here we successfully replace conventional Li-TFSI with Zn-TFSI2, which not only acts as a highly effective p-dopant but also enhances considerably both the photovoltaic performance and long-term stability. The incorporation of Zn-TFSI2 as a dopant for spiro-MeOTAD leads to an increase by one order in the hole mobility compared to Li-TFSI from 3.78 x 10(-3) cm(2) V-1 s(-1) to 3.83 x 10(-2) cm(2) V-1 s(-1). Furthermore, the device with Zn-TFSI2 showed an 80 mV higher built-in voltage and a bigger recombination resistance than the one with Li-TFSI, which were responsible for the striking increase in both the open-circuit voltage and fill factor, leading to a stabilized PCE of 22.0% for the best cells. Remarkably, the device employing Zn-TFSI2 demonstrated superb photo-stability, showing even a 2% increase in the PCE after 600 h light soaking at the maximum power point (mpp) under full sun, while the PCE of the device with Li-TFSI decreased by 20% under the same conditions. Similarly, the device with Zn-TFSI2 showed better operational stability at 50 degrees C resulting in a 21% decrease in the PCE after 100 h aging at the mpp under full sun while the Li-TFSI based one showed a 55% decrease. Moreover, the Zn-TFSI2 based device was capable of effectively resisting humidity compared to the one based on Li-TFSI from shelf stability monitoring (R.H. 40%) in the dark.Coporate Research and Technology Siemens AG, Germany; GRAPHENE Flagship Core 2 project - European Commission H2020 Programme [785219]; TUBITAK - 2214-A International Doctoral Research Fellowship Programme; NRP 70 "Energy Turnaround"This work was supported by a grant from Coporate Research and Technology Siemens AG, Germany. H.-S. K thanks the financial support from the GRAPHENE Flagship Core 2 project supported by the European Commission H2020 Programme under contract 785219 is gratefully acknowledged. J.-Y. S thanks the financial support from the NRP 70 "Energy Turnaround". S. A. would like to thank TUBITAK - 2214-A International Doctoral Research Fellowship Programme, for supporting his research at EPFL