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

Developmental Trajectories of Pediatric Obsessive–Compulsive Symptoms

Children who experience obsessive–compulsive symptoms (OCS) may be at risk for developing Obsessive–Compulsive Disorder (OCD). The current study aimed to investigate developmental trajectories of OCS, as well as possible predictors, within a community-based sample of children. Children (N = 1147) from the longitudinal NICHD Study of Early Child Care and Youth Development (SECCYD) were assessed for OCS, via the Child Behavioral Checklist – Obsessive–Compulsive Scale (OCS-8), eight times between Pre-Kindergarten (54 months; Pre-K) and High School (15 years of age; HS.) Participants were recruited within the United States and included only maternal caregivers. Preliminary analyses indicated that approximately 3% of the sample was above the diagnostic cutoff score on the OCS-8 at the High School time-point. Latent growth models tested symptom trajectories. Findings demonstrated three groups of OCS trajectories. Most children fell within a low symptomatology group (the No Peak group) with low OCS across all time points. Two additional OCS trajectories were also demonstrated: Pre-K Peak (high to low OCS across time) and HS Peak (low to high OCS across time). Both higher attention problems and greater depression/anxiety symptoms at the Pre-K time point predicted children’s membership in the Pre-K Peak or HS Peak groups compared to the No Peak group. Membership within the HS Peak group predicted a high likelihood of children’s OCS being above previously established cutoff scores for an OCD diagnosis at age 15 years. Membership within either the Pre-K Peak or No Peak groups predicted a low likelihood. This study provides new evidence for the existence of different developmental trajectories for youth with OCS. From a clinical perspective, these results may have important implications when considering the identification and early intervention of childhood OCS and OCD within the community

Search for high-energy neutrinos from gravitational wave event GW151226 and candidate LVT151012 with ANTARES and IceCube

The Advanced LIGO observatories detected gravitational waves from two binary black hole mergers during their first observation run (O1). We present a high-energy neutrino follow-up search for the second gravitational wave event, GW151226, as well as for gravitational wave candidate LVT151012. We find two and four neutrino candidates detected by IceCube, and one and zero detected by Antares, within �500s around the respective gravitational wave signals, consistent with the expected background rate. None of these neutrino candidates are found to be directionally coincident with GW151226 or LVT151012. We use nondetection to constrain isotropic-equivalent high-energy neutrino emission from GW151226, adopting the GW event�s 3D localization, to less than 2�10^51�2�10^54??ergby Anand Sengupta et al