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

Cohort profile: the COVID-19 Coping Study, a longitudinal mixed-methods study of middle-aged and older adults’ mental health and well-being during the COVID-19 pandemic in the USA

Purpose The COVID-19 pandemic, beginning in early 2020, has resulted in massive social, economic, political and public health upheaval around the world. We established a national longitudinal cohort study, the COVID-19 Coping Study, to investigate the effects of pandemic-related stressors and changes in life circumstances on mental health and well-being among middle-aged and older adults in the USA.Participants From 2 April to 31 May 2020, 6938 adults aged ≥55 years were recruited from all 50 US states, the District of Columbia and Puerto Rico using online, multi-frame non-probability-based sampling.Findings to date Mean age of the baseline sample was 67.3 years (SD: 7.9 years) and 64% were women. Two in three adults reported leaving home only for essential purposes in the past week (population-weighted proportion: 69%; 95% CI: 68% to 71%). Nearly one in five workers aged 55–64 years was placed on a leave of absence or furloughed since the start of the pandemic (17%; 95% CI: 14% to 20%), compared with one in three workers aged ≥75 years (31%; 95% CI: 21% to 44%). Nearly one-third of adults screened positive for each of depression (32%; 95% CI: 30% to 34%), anxiety (29%; 28% to 31%) and loneliness (29%; 95% CI: 27% to 31%), with decreasing prevalence of each with increasing age.Future plans Monthly and annual follow-ups of the COVID-19 Coping Study cohort will assess longitudinal changes to mental health, cognitive health and well-being in relation to social, behavioural, economic and other COVID-19-related changes to life circumstances. Quantitative and in-depth qualitative interview data will be collected through online questionnaires and telephone interviews. Cohort data will be archived for public use