On preparing for the great gift of community that climate disasters can give us

There is a widespread (if rarely voiced) assumption, among those who dare to understand the future which climate chaos is likely to yield, that civility will give way and a Hobbesian war of all against all will be unleashed. Thankfully, this assumption is highly questionable. The field of ‘Disaster Studies’, as shown in Rebecca Solnit’s A Paradise Built in Hell, makes clear that it is at least as likely that, tested in the crucible of back-to-back disasters, humanity will rise to the challenge, and we will find ourselves manifesting a truer humanity than we currently think ourselves to have. Thus the post-sustainability world will offer us a tremendous gift amidst the carnage. But how well we realise this gift depends on our preparing the way for it. In order to prepare, the fantasy of sustainable development needs to be jettisoned, along with the bargain-making mentality underpinning it. Instead, the inter-personal virtues of generosity, fraternity and care-taking need fostering. One role a philosophically informed deep reframing can play in this process of virtuous preparation for disaster is in helping people to understand that, in order to care for their children, they need to care for their children in turn, and so on, ad infinitum

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

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