The Significance of Cell-related Challenges in the Clinical Application of Tissue Engineering.

Tissue engineering is increasingly being recognized as a new approach that could alleviate the burden of tissue damage currently managed with transplants or synthetic devices. Making this novel approach available in the future for patients who would potentially benefit is largely dependent on understanding and addressing all those factors that impede the translation of this technology to the clinic. Cell-associated factors in particular raise many challenges, including those related to cell sources, up- and downstream techniques, preservation, and the creation of in vitro microenvironments that enable cells to grow and function as far as possible as they would in vivo. This paper highlights the main confounding issues associated with cells in tissue engineering and how these issues may hinder the advancement of therapeutic tissue engineering. This article is protected by copyright. All rights reserved

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

The paradox of power in a People\u27s Republic of China middle school

This study is an ethnography of a middle school located in the People\u27s Republic of China and is based upon 13 months of fieldwork conducted in China in 1989-1989. The study focuses on the teacher/student relationship and the way in which that relationship is shaped by Chinese cultural values pertaining to face, criticism, and evaluation. The study found that evaluation of others\u27 ability and morality plays a very important role both inside and outside the classroom in China. In schools the orientation to evaluation even influences pedagogy, since one frequent goal of teaching is to teach students the ability to identify and analyze that which is meritorious. Evaluation also often takes the form of criticism. At Third Affiliated Middle School, the school studied, students accused of serious offenses are disciplined by being criticized in front of the entire school. If teachers are incompetent or deemed to be immoral, they too can become the victims of criticism by their students. Students frequently complain about their teachers to each other and in meetings held at the school to allow students to evaluate their teachers. Sometimes students criticize teachers publicly, during class. Such criticism by students of teachers occurred often during the Cultural Revolution, but this study concluded that the phenomenon of those of inferior status criticizing their superiors has much deeper historical and cultural roots. Face, and its use for purposes of social control in homes, schools, and the workplace, depends on people making judgements of each other. This gives a certain legitimacy even to the evaluations inferiors make of their superiors. In addition the performative nature of face and status in China means that superiors are more likely to be on stage as the evaluative targets, with those of lesser status as the audience and evaluators. The result is a paradox of power, in which those of higher status are watched more closely than others and hence are more vulnerable to losing face and status if they act incompetently or immorally