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

Whistleblowing

(Statement of Responsibility) by Monica Gaughan(Thesis) Thesis (B.A.) -- New College of Florida, 1989(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Lewis, Eugen

National science training policy and early scientific careers in France and the United States

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Scientists’ Participation in University Research Centers: What are the Gender Differences?

University-affiliated multidisciplinary research centers have grown in importance in academia. Most research to-date has focused on these centers from an institutional perspective, with recent work only beginning to explore the ways in which such centers affect the development of academic careers. Hence, little is known about how scientists who are center-affiliated differ from those who are not affiliated. Clearly, both selection and influence effects may be expected to operate in terms of research productivity, timing, and resources. A further puzzle is how center affiliation may differ between male and female scientists. In this study, we use a new, nationally representative dataset of scientists and engineers working in Carnegie Research Extensive universities to develop an understanding of how center-affiliated scientists differ from exclusively department-based academic scientists and engineers, and investigate the extent to which gender moderates the effects of centers. As expected, our national sample shows that women are younger, whiter, less likely to be tenured, and at a lower rank than their male colleagues. We find that women are as likely to join centers as men, and do so at a similar stage in their career. Most of the male–female differences observed in disciplinary settings are sustained in centers, but women appear to have greater research equality in them (compared to the departmental setting). In particular, men and women in centers spend the same amount of time writing grant proposals, conducting both grant-supported and unfunded research, and administering grants. This suggests that centers may constitute an institutional context in which some aspects of gender equity in science may be achieved. Copyright Springer Science+Business Media, Inc. 2005

Track 2 GK-12: STEP Up!

Issued as final reportNational Science Foundation (U.S.