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

Four worlds of writing

xviii, 423 p.; 23 cm

Four worlds of writing

xvi, 576 p. : ill. ; 23 cm

Invention In Contemporary Rhetoric: Heuristic Procedures.

Doctor of Education (EdD)LiteratureModern literatureUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/179799/2/6807656.pd

Understanding Persuasive Essay Writing: Linguistic/Rhetorical Approach

This item submitted to IUPUI ScholarWorks as part of the OASIS Project. Article reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Permission granted through posted policies on copyright owner’s website or through direct contact with copyright owner.This paper reports on research, funded by the Educational Foundation of the Exxon Corporation, to study several measures for describing and evaluating student persuasive writing. The variables examined were coherence, cohesion, syntactic features, and persuasive appeals. The data were 100 American and British high-school student persuasive essays randomly selected from the compositions of the International Education Association project. The results demonstrate the need for a multidimensional methodology to assess a broad range of linguistic and rhetorical features in order to adequately account for variation in writing quality among students

Problem-Solving: The Debates in Composition and Psychology

&apos;s debate about problem-solving is one of the most interesting controversies in composition literature. Sparked by Lauer&apos;s CoUegeCompositionand Communication article, &quot;Heuristics and Composition,&quot; the exchange includes several essays by Berthoff as well as responses and counter-responses by both writers. Lauer asserts, &quot;Unless both the testmakers and the teachers of composition investigate beyond the field of English, beyond even the area of rhetorical studies for the solution to the composition problem, they will find themselves wandering in an endless maze&quot; (396). In rebuttal, Berthoff warns of the dangers of using problemsolving as a pedagogical tool. In &quot;The Problem of Problem Solving&quot; she cautions, &quot;When we make problem-solving central to a philosophy of education we effectively separate learning from knowing: the results are philosophically disastrous and politically dangerous&quot; (240). Even though this exchange occurred in the seventies, Berthoff&apos;s and Lauer&apos;s dialogue is still intriguing and important as well as relevant to more recent arguments about problem-solving in composition literature and in psychological studies. As Lauer&apos;s bibliography indicates, psychologists pioneered the study of and continue to investigate problem-solving. However, psychologists have not always agreed about the nature and usefulness of problemsolving. In fact, the history of twentieth-eentury psychology can be traced by outlining different psychological views of problem-solving. Similarly, even composition theorists who agree on its usefulness in teaching writing have not always held identical views about what problem-solving is. In this essay, we will delineate various conceptions of and arguments about problem-solving and propose a means for dealing with these conflicts. First, we outline several ways writing specialists who advocate problem-solving have viewed it; second, we discuss the criticisms of those who, along with Berthoff, find fault with using problem-solving in composition instructions; third, we propose resolving some of these conflicts by viewing problemsolving from the perspective of an internal-extemal validity continuum; and fourth, we examine arguments in the psychological problem-solving literature which parallel the disagreements in composition studies. This review should lead to a better understanding of the issues surrounding problem-solving, both in theory and practice

Cost-Effectiveness Analysis of Breast Cancer Control Interventions in Peru

Objectives: In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context. Methods: We performed a cost-effectiveness analysis (CEA) according to WHO-CHOICE guidelines, from a healthcare perspective. Different screening, early detection, palliative, and treatment interventions were evaluated using mathematical modeling. Effectiveness estimates were based on observational studies, modeling, and on information from Instituto Nacional de Enfermedades Neoplásicas (INEN). Resource utilizations and unit costs were based on estimates from INEN and observational studies. Cost-effectiveness estimates are in 2012 United States dollars (US$) per disability adjusted life year (DALY) averted. Results: The current breast cancer program in Peru ($8,426 per DALY averted) could be improved through implementing triennial or biennial screening strategies. These strategies seem the most cost-effective in Peru