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

Secondary Deuterium Isotope Effects in Radical Reactions

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Religion and the right to (dispose of) life: A study of the attitude of Christian, Muslim and Hindu students in India concerning death penalty, euthanasia and abortion

Item does not contain fulltextThe debate over death penalty, euthanasia and abortion reached a climax during the second half of the twentieth century. It brings into focus the underlying contrasting currents of right to life and right to dispose of life. The pluralistic Indian context in its turn can add to the ambivalent relationship between religion and the (non-)disposability of life. Hence, the question that we address in this paper concerns the role religions play in soliciting and legitimizing the (non-)disposability of life. Our empirical research, among 1215 Christian, Muslim and Hindu college students in Tamil Nadu, focuses on the possible impact of personal religious attitude, contextual religious attitude, and the value of human dignity, on the perception of right to life in the face of death penalty, euthanasia, and abortion. Overall, we find that the three religious groups manifest opposition to disposal of life by death penalty, and an uncertain openness to disposal of life by euthanasia and abortion for victim’s sake. However, as regards euthanasia, while Christians and Hindus tend to be open to disposal of life, Muslims tend to be uncertain. As regards abortion for psycho-economic reasons, the tendency among Christians is non-disposal of life and the tendency among Hindus and Muslims is an uncertain openness to disposal of life. In dealing with the complex issue of (non-)disposal of life, our findings related to personal and contextual religious attitude suggest that religions can provide a meta-ethical basis for both ‘sacredness’ and ‘quality’ human life