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

Collaborative imagination synchronizes representations of the future and fosters social connection in the present

From close friends to people on a first date, imagining a shared future appears fundamental to relationships. Yet, no previous research has conceptualized the act of imagination as a socially constructed process that affects how connected we feel to others. The present studies provide a framework for investigating imagination as a collaborative process in which individuals cocreate shared representations of hypothetical events—what we call collaborative imagination. Across two preregistered studies (N = 244), we provide evidence that collaborative imagination of a shared future fosters social connection in novel dyads—beyond imagining a shared future individually or shared experience in general. Subjective ratings and natural language processing of participants’ imagined narratives illuminate the representational features of imagined events shaped by collaborative imagination. Together, the present findings have the potential to shift how we view the structure and function of imagination with implications for better understanding interpersonal relationships and collective cognition

Spatial ecology and habitat use of two-spined blackfish Gadopsis bispinosus in an upland reservoir

The scale and patterns of movement and habitat use are primary considerations in the conservation and management of threatened species. Movement, activity and habitat use of the threatened two-spined blackfish Gadopsis bispinosus were assessed in a small upland reservoir in south-eastern Australia using manual and remote radio-telemetry. Movements and activity of two-spined blackfish (n = 19) were studied over a 28-day period and exhibited proportionately large directional crepuscular movement and activity with heightened activity continuing throughout the night (although movement was subdued). Two daily movement strategies were observed: movements from diurnal home-shelter habitats (predominantly rock) to macrophytes at night (14 individuals), and occupation of macrophytes during the entire diel period and restricted movement (five individuals). Daily movement strategies were fixed (not plastic) among all individuals, with one exception, for the duration of the study period. Rock, fallen timber and macrophytes were the most commonly used daytime shelter habitat (in order of preference). Although some information exists on movements and habitat use of this species and the congeneric river blackfish G. Marmoratus in lotic environments, we present the first study of movements and habitat use for either species in lentic environments. Given the occupation of lentic environments by this threatened species, the data presented in this study provide insight into the habitat requirements for this species, and offer opportunities for habitat enhancement in existing reservoirs within the species' geographic range