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

Are Migratory Birds More Likely to Collide With North-Facing and South-Facing Windows?

Bird populations have declined dramatically since 1970 with an estimated population loss of 2.9 billion breeding adults. One of the top causes of direct anthropogenic mortality is collisions with buildings. Low- and high-rise buildings represent approximately 56% of window-collision mortalities. As urban environments expand, bird-building collisions are expected to increase. Therefore, the implementation of preventative strategies is important to curtail the further loss of bird population and diversity. Several deterrents of window collisions have proved effective. Windows can be made more visible to birds through the use of netting, screens, decals, and special glass with embedded UV-reflecting patterns. Because cost and aesthetic preferences may be barriers to implementation, it would be helpful to know if widows facing in certain directions are more likely to involve collisions. I used window collision data collected in and around Atlanta, Georgia to determine whether migrating birds are more likely to collide with windows that face north in the fall (when birds are flying south) or south in the spring (when birds are flying north). We will present data testing whether migratory bird species are more likely to collide with buildings than resident species, as well as whether north-facing or south-facing windows are more frequently associated with bird-window collisions. Results from this study will provide key information about where collision deterrents should be prioritized on building in future conservation efforts

Menopause Analytical Hormonal Correlate Outcome Study (MAHCOS) and the association to brain electrophysiology (P300) in a clinical setting.

Various studies have demonstrated that increased leptin levels and obesity are inversely related to cognitive decline in menopausal women. It is hypothesized that adiposity is inversely correlated with cognitive decline, as women with increased weight are less vulnerable to diminishing cognition. However, it is increasingly observed that menopausal women, even with increased adiposity, experience significant cognitive decline. Positron emission tomography (PET) has been used to analyze cognitive function and processing in menopausal women. Evoked potentials (P300) and neurophysiologic tests have validated brain metabolism in cognitively impaired patients. Post-hoc analyses of 796 female patients entering PATH Medical Clinic, between January 4, 2009 and February 24, 2013, were performed as part of the "Menopause Analytical Hormonal Correlate Outcome Study" (MAHCOS). Patient age range was 39-76 years (46.7 ± 0.2). P300 latency and amplitude correlated with a number of hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, estrone, estriol, DHEA, pregnenolone, progesterone, free and total testosterone, thyroid stimulating hormone (TSH), Vitamins D 1.25 and D 25OH, leptin, and insulin-like growth factor-binding protein 3 (IGF-BP3). Corrected statistics did not reveal significant associations with P300 latency or amplitude for these hormones except for leptin plasma levels. However, factor analysis showed that FSH and LH clustered together with Vitamin D1.25 and Vitamin D25OH, P300 latency (not amplitude), and log leptin were found to be associated in the same cluster. Utilizing regression analysis, once age adjusted, leptin was the only significant predictor for latency or speed (p = 0.03) with an effect size of 0.23. Higher plasma leptin levels were associated with abnormal P300 speed (OR = 0.98). Our findings show a significant relationship of higher plasma leptin levels, potentially due to leptin resistance, and prolonged P300 latency. This suggests leptin resistance may delay electrophysiological processing of memory and attention, which appears to be the first of such an association

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Principal Component Analysis in the Log Scale Correlations Estimated by Pairwise Method.

<p>Principal Component Analysis in the Log Scale Correlations Estimated by Pairwise Method.</p

Association between FSH and Estradiol, Estrone, Estriol for FSH under 40.

<p>Association between FSH and Estradiol, Estrone, Estriol for FSH under 40.</p

P300 Speed Variables predicted by Leptin with Age (logistic).

<p>P300 Speed Variables predicted by Leptin with Age (logistic).</p

K-Means Clustering Analysis Cluster Bi-Plot in 3D.

<p>K-Means Clustering Analysis Cluster Bi-Plot in 3D.</p

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Latency Variables predicted by Leptin with Age (ANOVA).

<p>Latency Variables predicted by Leptin with Age (ANOVA).</p