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

Stigma, HIV and health: a qualitative synthesis

Background: HIV-related stigma continues to negatively impact the health and well-being of people living with HIV, with deleterious effects on their care, treatment and quality of life. A growing body of qualitative research has documented the relationship between HIV-related stigma and health. This review aims to synthesize qualitative evidence that explored the intersections of stigma and health for people with HIV. Methods: A thematic summary was conducted that was guided by the qualitative metasummary technique developed by Sandelowski and Barraso. Literature searches yielded 8,622 references of which 55 qualitative studies were identified that illustrated HIV-related stigma in the context of health. Results: The metasummary classified qualitative findings into three overarching categories: conceptualizing stigma which identified key dimensions of HIV-related stigma; experiencing stigma which highlighted experiences of stigma in the health context, and managing stigma which described ways in which stigma is avoided or addressed. To better illustrate these connections, the qualitative literature was summarized into the following themes: stigma within health care settings, the role of stigma in caring for one's health, and strategies to address HIV-related stigma in the health context. A number of health care practices were identified - some rooted in institutional practices, others shaped by personal perceptions held by practitioners - that could be stigmatizing or discriminatory towards people with HIV. There existed interconnections between enacted stigma and felt stigma that influenced health care utilization, treatment adherence, and overall health and well-being of people with HIV. Intersectional stigma also emerged as instrumental in the stigma experiences of people living with HIV. A number of strategies to address stigma were identified including social support, education, self-efficacy, resilience activities, and advocacy. Conclusion: This review of the qualitative evidence indicates that HIV-related stigma within health contexts is a broad social phenomenon that manifests within multiple social spheres, including health care environments. Findings from this review indicate that future stigma research should consider the social structures and societal practices - within and outside of health care environments - that perpetuate and reinforce stigma and discrimination towards people with HIV

Animal population decline and recovery after severe fire: Relating ecological and life history traits with expert estimates of population impacts from the Australian 2019-20 megafires

Catastrophic megafires can increase extinction risks identifying species priorities for management and policy support is critical for preparing and responding to future fires. However, empirical data on population loss and recovery post-fire, especially megafire, are limited and taxonomically biased. These gaps could be bridged if species' morphological, behavioural, ecological and life history traits indicated their fire responses. Using expert elicitation that estimated population changes following the 2019–20 Australian megafires for 142 terrestrial and aquatic animal species (from every vertebrate class, one invertebrate group), we examined whether expert estimates of fire-related mortality, mortality in the year post-fire, and recovery trajectories over 10 years/three generations post-fire, were related to species traits. Expert estimates for fire-related mortality were lower for species that could potentially flee or shelter from fire, and that associated with fire-prone habitats. Post-fire mortality estimates were linked to diet, diet specialisation, home range size, and susceptibility to introduced herbivores that damage or compete for resources. Longer-term population recovery estimates were linked to diet/habitat specialisation, susceptibility to introduced species species with slower life histories and shorter subadult dispersal distances also had lower recovery estimates. Across animal groups, experts estimated that recovery was poorest for species with pre-fire population decline and more threatened conservation status. Sustained management is likely needed to recover species with habitat and diet specialisations, slower life histories, pre-existing declines and threatened conservation statuses. This study shows that traits could help inform management priorities before and after future megafires, but further empirical data on animal fire response is essential