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

Power, responsibility, and justice in research with Indigenous communities

Cultural context is necessary for students to build connections and conduct responsible research on their Interactive Qualifying Project (IQP), especially with regards to Indigenous communities, and this is not adequately provided in the current preparation phase of the IQP. To supplement existing resources, we created the Just IQP Research website for ethical partnership with Māori communities, using insights from our research including interviews with past IQP students, advisors, and scholars in New Zealand who have collaborated with the Indigenous Māori population. The website, wp.wpi.edu/justiqpresearch, focuses on 6 key concepts that emerged from our research: culture and history, language, reflection, discomfort, ethical listening, and accountability

Flag on the Play: Using Technology to Tackle Self Reporting of Concussions in Collegiate Football

https://digitalcommons.wpi.edu/gps-posters/1715/thumbnail.jp

Automatic Feeding Device for Premature Infants in Low to Middle Income Countries

Low-to-middle income countries (LMICs) have a high percentage of preterm and low birth-weight (LBW) infants. These infants need special care to reduce risk of infant mortality and underdevelopment but resources are scarce. An automatic, affordable, lightweight and user-friendly feeding device would allow clinicians in LMICs to feed LBW infants a prescribed volume while minimizing exhausted resources. The concept of the device is a sensor to measure volume delivered and to pinch tubing when the specified volume is delivered. The user interface was used to select a desired volume of fluid between 2-10 mL delivered with a percent error of less than 10% for water, milk and formula. The device was evaluated by clinicians and engineers in Ghana, who gave valuable feedback to improve the device

Low prepregnancy adiponectin concentrations are associated with a marked increase in risk for development of gestational diabetes mellitus.

ObjectiveTo examine whether circulating total and high-molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM).Research design and methodsThis was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984-1996) with a serum sample obtained and who had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies.ResultsCompared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7-2.9], 3.7 [1.9-7.2], and 5.2 [2.6-10.1]; P(trend) &lt;0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P(trend) &lt;0.001). The combined effects of having total adiponectin levels below the median (&lt;10.29 mg/mL) and being overweight or obese (BMI ≥25.0 kg/m(2)) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6-12.5]).ConclusionsPrepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention