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

Teaching Students to Evaluate Quantitative Evidence

This workshop facilitated by Dr. Judith Canner of the Department of Mathematics and Statistics guided participants in considering the uses of data, developmental approaches to working with data, and frameworks for evaluating data from different disciplinary perspectives. Dr. Canner also demonstrated strategies for teaching students to engage with data, using articles in the news.https://digitalcommons.csumb.edu/ta_workshops/1001/thumbnail.jp

Threshold Concepts in Quantitative Reasoning

The idea of “threshold concepts” has been used to identify discipline-based concepts that are critical to that academic area. Threshold concepts are often difficult for students to assimilate in a meaningful way but, once done, can be powerful for the learner. In general, threshold concepts are 1) transformative to learner thinking; 2) bounded by the discipline; 3) integrative with other concepts; and 4) irreversible once understood (Meyer and Land 2003). This paper presents five threshold concepts in quantitative reasoning (QR) developed by transdisciplinary faculty workgroups that may be applicable for non-mathematics disciplines as well. They are as follows: 1) QR is an iterative process; 2) Abstract patterns can represent relationships between variables or objects; 3) There is a bidirectional translation between the concrete and the abstract; 4) Effective comparison depends on proportional reasoning; and 5) Different visual representations can communicate varying perspectives on the same quantitative information. The purpose of this paper is twofold: to explore and justify the proposed concepts as threshold concepts in QR-based courses and to offer practical examples which might assist students in developing and understanding these proposed threshold concepts