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

Induction of Chirality in Two-Dimensional Nanomaterials: Chiral 2D MoS₂ Nanostructures

Two-dimensional (2D) nanomaterials have been intensively investigated due to their interesting properties and range of potential applications. Although most research has focused on graphene, atomic layered transition metal dichalcogenides (TMDs) and particularly MoS₂ have gathered much deserved attention recently. Here, we report the induction of chirality into 2D chiral nanomaterials by carrying out liquid exfoliation of MoS₂ in the presence of chiral ligands (cysteine and penicillamine) in water. This processing resulted in exfoliated chiral 2D MoS₂ nanosheets showing strong circular dichroism signals, which were far past the onset of the original chiral ligand signals. Using theoretical modeling, we demonstrated that the chiral nature of MoS₂ nanosheets is related to the presence of chiral ligands causing preferential folding of the MoS₂ sheets. There was an excellent match between the theoretically calculated and experimental spectra. We believe that, due to their high aspect ratio planar morphology, chiral 2D nanomaterials could offer great opportunities for the development of chiroptical sensors, materials, and devices for valleytronics and other potential applications. In addition, chirality plays a key role in many chemical and biological systems, with chiral molecules and materials critical for the further development of biopharmaceuticals and fine chemicals, and this research therefore should have a strong impact on relevant areas of science and technology such as nanobiotechnology, nanomedicine, and nanotoxicology

Measurement of the Ωc0\Omega_c^0 lifetime at Belle II

We report on a measurement of the $\Omega_c^0$ lifetime using $\Omega_c^0 \to \Omega^-\pi^+$ decays reconstructed in $e^+e^-\to c\bar{c}$ data collected by the Belle II experiment and corresponding to $207~{\rm fb^{-1}}$ of integrated luminosity. The result, $\rm\tau(\Omega_c^0)=243\pm48( stat)\pm11(syst)~fs$, agrees with recent measurements indicating that the $\Omega_c^0$ is not the shortest-lived weakly decaying charmed baryon

Measurement of the Ωc0\Omega_c^0 lifetime at Belle II

We report on a measurement of the $\Omega_c^0$ lifetime using $\Omega_c^0 \to \Omega^-\pi^+$ decays reconstructed in $e^+e^-\to c\bar{c}$ data collected by the Belle II experiment and corresponding to $207~{\rm fb^{-1}}$ of integrated luminosity. The result, $\rm\tau(\Omega_c^0)=243\pm48( stat)\pm11(syst)~fs$, agrees with recent measurements indicating that the $\Omega_c^0$ is not the shortest-lived weakly decaying charmed baryon