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

'Qu'est-ce que la critique': La Boétie, Montaigne, Foucault

Essayist Michel de Montaigne is one of the most accessible and widely read authors in world literature. His skepticism and relativism, and the personal quality of his writing, make him a perennial favorite among readers today. Montaigne After Theory / Theory After Montaigne pursues the idea that theory has altered the scholarly understanding of Montaigne, while Montaigne's ideas have simultaneously challenged the authority of the various interpretive doxa collectively known as "theory." Montaigne's life and writings have drawn myriad interpretations. While some scholars of his work focus on the content of the writings to define the man, others stress his playful use of language. Montaigne's complex and multifaceted works provide fertile ground for exploring themes of wide-ranging significance within the field of literary theory, including the relationship between biography and theory; the critique of modernism; a critical history of the confessional mode of writing; sexuality and gender; and the theory of practice. The essays in this collection move beyond the current stalemate in Montaigne criticism by revisiting questions about the role of theory in literary studies and by opening up a dialogue on the validity and limitations, or use and abuse, of theory in Montaigne studies

Voluntary Servitude and the Erotics of Friendship: From Classical Antiquity to Early Modern France

Focusing primarily on three early modern French authors, this book explores the erotics and politics of "voluntary servitude" in classical antiquity and the early modern period. These authors-Étienne de La Boétie, Michel de Montaigne, and Marie de Gournay-pursue related inquiries into voluntary servitude and self-control in marriage, friendship, pederasty and politics. Marc Schachter shows how Montaigne's intimate textual relationship with La Boétie provides him the opportunity to honor his beloved friend while transforming many of his ideas. Similarly, Marie de Gournay's editorial voluntary servitude to Montaigne provides her the occasion to authorize her own practice as a woman author and to engage critically with Montaigne's ideas even as she celebrates her friendship with him. Schachter's analyses are pursued particularly through the lens of Michel Foucualt's concept of governmentality which, like voluntary servitude, operates on three interrelated scales: self-control, control in interpersonal relationships, and political control. Schachter argues that thinking about the function of voluntary servitude through the lens of governmentality leads to a more nuanced understanding both of Foucault's late work and of the transformational possibilities offered by friendship and voluntary servitude in early modern France

Some Notes on the Print History of Illustrated Italian Editions of Apuleius' Golden Ass

The 177 essays in these two richly illustrated volumes represent the cutting edge of Italian Renaissance scholarship in nearly every one of its fields and were gathered to honor Joseph Connors, Director of Villa I Tatti from 2002 to 2010. Demonstrating I Tatti’s pivotal role as the world’s leading center for Italian Renaissance studies, the essays cover all the branches of art history, as well as many aspects of political, economic, and social history, literature, and music, from the early Renaissance to the eighteenth century. Appropriately, the volumes also include a selection of contributions devoted to Bernard Berenson and his legacy as both a collector and a scholar. Each of the authors—a group representing dozens of countries—was a Fellow or associate of the Harvard University Center for Italian Renaissance Studies during the eight years in which Connors served as Director

Platonic Love in Renaissance Discussions of Friendship

Elite friendship discourse in the Renaissance was shaped by a set of commonplaces inherited from classical antiquity according to which friends were virtuous, male, and few in number, and their relationships egalitarian and non-sexual. Neoplatonic love had the power to disrupt many of these received ideas. Ficino’s account of male friendship in his Lysis commentary emphasized the importance of spiritual desire in initiating relationships and foregrounded a pedagogical dimension more in keeping with a chaste version of Greek pederasty than the non-hierarchical models of friendship inherited from Aristotle and Cicero. In a poem on the Platonic androgyne, Antoine Héroët used the language of friendship to describe heterosexual unions as offering a potential step towards union with God. Bonaventure des Périers warned instead of the dangers of earthly erotic entanglements in a verse commentary to his translation of Plato’s Lysis, thereby concurring with the beliefs of his benefactor Marguerite de Navarre while suggesting that female community might offer the soul some solace before death provided the possibility of joining with God. Finally, Montaigne’s unorthodox account of his relationship with his deceased friend La Boétie engaged with the Neoplatonic tradition while eschewing the possibility it might facilitate spiritual ascent

'Quanto concede la Guerra': Epic Masculinity and the Education of Desire in Tasso's Gerusalemme Liberata

The idea that masculinity has a history is fairly recent. This collection opens new paths in literary and theatre studies by addressing not only how literary texts represented masculinity but how different representational strategies in such texts produce masculinity. They thus offer provocative answers to the question of what it meant to be a “man” on the newly global stage. While the volume as a whole offers a new way of thinking about literary histories, the individual articles offer reflections on the relationship between gendered meanings and the sophisticated, self-conscious, representational form of language that is called literature. What is especially innovative about this collection is its success in moving beyond the obvious cultural focus of the topic to consider how literary genre also affected the way masculinity was viewed. Such an approach brings a fresh perspective on current debates about the nature, extent and contemporary meaning of male/male sexual practices in the pre-modern and early modern period