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

Personality and Substance Use in Mexicans and Mexican-Americans

Within the theoretical framework of the five-factor model of personality, existing research identifies personality profiles significantly related to certain at-risk behaviors, such as substance use and poor health outcomes. Among Latinos, there is limited knowledge on whether personality traits are associated with substance use behaviors. This study uses a sample of Mexican (N = 323) and Mexicans American (N = 1,143) participants to examine the interplay of culture and personality differences in relation to substance use and alcohol dependence. Mexican Americans reported higher use of cocaine and marijuana, while Mexicans were more likely to report cigarette smoking. Lower Agreeableness and Conscientiousness were associated with a higher likelihood of substance use and alcohol dependence. Higher Extraversion was associated with higher likelihood of substance use, Openness with marijuana use, and for Neuroticism the associations differed across cultural groups and drug-type used. The study identified cross-cultural communalities and differences in personality traits related to drug use and dependence

Rater wealth predicts perceptions of outgroup competence

a b s t r a c t National income has a pervasive influence on the perception of ingroup stereotypes, with high status and wealthy targets perceived as more competent. In two studies we investigated the degree to which economic wealth of raters related to perceptions of outgroup competence. Raters&apos; economic wealth predicted trait ratings when (1) raters in 48 other cultures rated Americans&apos; competence and (2) Mexican Americans rated Anglo Americans&apos; competence. Rater wealth also predicted ratings of interpersonal warmth on the culture level. In conclusion, raters&apos; economic wealth, either nationally or individually, is significantly associated with perception of outgroup members, supporting the notion that ingroup conditions or stereotypes function as frames of reference in evaluating outgroup traits. Published by Elsevier Inc

The association between personality traits and body mass index varies with nativity among individuals of Mexican origin

•Personality traits were associated with BMI in ways consistent with the literature.•Some associations were moderated by nativity in this sample of Mexican origin.•Impulsivity was more strongly related to BMI for 2nd generation Mexican-Americans.•Impulsivity was less strongly related to BMI for Mexicans living in Mexico.•Conscientiousness was associated with lower BMI regardless of nativity. Personality traits have been associated consistently with health-related outcomes, but less is known about how aspects of the sociocultural environment modify these associations. This study uses a sample of participants of Mexican origin (N = 1013) to test whether exposure to the United States, indexed by nativity (Mexicans living in Mexico, foreign-born Mexican Americans, and U.S.-born Mexican Americans), moderates the association between personality traits and body mass index (BMI). Higher Conscientiousness was associated with lower BMI, regardless of nativity. In contrast, the association between Neuroticism and BMI was moderated by exposure to the U.S.: Neuroticism was associated with higher BMI among U.S.-born Mexican Americans (partial r = .15) but not among Mexican participants (partial r = .00), an effect strongest and most robust for the impulsivity facet of Neuroticism. This finding suggests that with more exposure to the United States, those who are more emotionally impulsive are at greater risk for obesity. More broadly, these findings suggest that social and psychological vulnerabilities interact to contribute to health outcomes