Ver Sacrum (“Printemps sacré”), la revue de la Sécession viennoise : Affiche

Le groupe de la Sécession viennoise mène plusieurs actions, parmi lesquelles la création de la revue Ver Sacrum (“Printemps sacré”), destinée à diffuser ces idées nouvelles

A new attack on alcoholism

Copy of an article A new attack on alcoholism by Alfred C. Roller published in the New York World Telegram, August 28, 1954 based on an interview with Selden D. Bacon

Briefe Hofmannsthals, Alfred Rollers und Eugen Kilians zur Uraufführung von Büchners "Wozzeck" am Münchener Residenztheater, 1913 / mitgeteilt und kommentiert von Dietmar Goltschnigg

Nach ersten knappen Hinweisen von Karl Dachs und Rudolf Hirsch haben Eugene Weber und Wolfdietrich Rasch ausführlicher dargelegt, daß die Uraufführung von Büchners "Wozzeck"-Tragödie am 8. November 1913 im Münchener Residenztheater maßgeblich durch Hofmannsthal angeregt worden ist, der den Text eingehend bearbeitet und dem Fragment sogar einen Schluß hinzugedichtet hat. Die Briefe, die er in diesem Zusammenhang an CIemens von Franckenstein geschrieben hat, wurden auszugsweise zunächst von Weber und Rasch und nunmehr vollständig durch Ulrike Landfester publiziert. - Außer diesem Briefwechsel gibt es zum Münchener "Wozzeck"-Projekt jedoch noch eine weitere Korrespondenz, und zwar zwischen Hofmannsthal und Alfred Roller, die im Folgenden - mit zwei Schreiben von Eugen Kilian an Roller - mitgeteilt werden soll

Und Ihr? Zeichnet 7. Kriegsanleihe

Poster shows a soldier in a trench holding a grenade. Text: And you? Subscribe to the 7th War Loan at the k.k. pr. Öst. Creditanstalt f.H.u.G.Forms part of: Rehse-Archiv für Zeitgeschichte und Publizistik.Signed with artist's monogram.Title from item

Progression of Lung Cancer is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors

Dysfunctional T cells present in malignant lesions are characterized by a sustained and highly diverse expression of inhibitory receptors, also referred to as immune checkpoints. Yet, their relative functional significance in different cancer types remains incompletely understood. In this study, we provide a comprehensive characterization of the diversity and expression patterns of inhibitory receptors on tumor-infiltrating T cells from patients with non-small cell lung cancer. In spite of the large heterogeneity observed in the amount of PD-1, Tim-3, CTLA-4, LAG-3, and BTLA expressed on intratumoral CD8(+) T cells from 32 patients, a clear correlation was established between increased expression of these inhibitory coreceptors and progression of the disease. Notably, the latter was accompanied by a progressively impaired capacity of T cells to respond to polyclonal activation. Coexpression of several inhibitory receptors was gradually acquired, with early PD-1 and late LAG-3/BTLA expression. PD-1 blockade was able to restore T-cell function only in a subset of patients. A high percentage of PD-1(hi) T cells was correlated with poor restoration of T-cell function upon PD-1 blockade. Of note, PD-1(hi) expression marked a particularly dysfunctional T-cell subset characterized by coexpression of multiple inhibitory receptors and thus may assist in identifying patients likely to respond to inhibitory receptor-specific antibodies. Overall, these data may provide a framework for future personalized T-cell-based therapies aiming at restoration of tumor-infiltrating lymphocyte effector functions

Expression of inhibitory receptors on intratumoral T cells modulates the activity of a T cell-bispecific antibody targeting folate receptor

T-cell bispecific antibodies (TCBs) are a novel therapeutic tool designed to selectively recruit T-cells to tumor cells and simultaneously activate them. However, it is currently unknown whether the dysfunctional state of T-cells, embedded into the tumor microenvironment, imprints on the therapeutic activity of TCBs. We performed a comprehensive analysis of activation and effector functions of tumor-infiltrating T-cells (TILs) in different tumor types, upon stimulation by a TCB targeting folate receptor 1 and CD3 (FolR1-TCB). We observed a considerable heterogeneity in T-cell activation, cytokine production and tumor cell killing upon exposure to FolR1-TCB among different FolR1-expressing tumors. Of note, tumors presenting with a high frequency of PD-1hi TILs displayed significantly impaired tumor cell killing and T-cell function. Further characterization of additional T-cell inhibitory receptors revealed that PD-1hi TILs defined a T-cell subset with particularly high levels of multiple inhibitory receptors compared with PD-1int and PD-1neg T-cells. PD-1 blockade could restore cytokine secretion but not cytotoxicity of TILs in a subset of patients with scarce PD-1hi expressing cells; in contrast, patients with abundance of PD-1hi expressing T-cells did not benefit from PD-1 blockade. Our data highlight that FolR1-TCB is a promising novel immunotherapeutic treatment option which is capable of activating intratumoral T-cells in different carcinomas. However, its therapeutic efficacy may be substantially hampered by a pre-existing dysfunctional state of T-cells, reflected by abundance of intratumoral PD-1hi T-cells. These findings present a rationale for combinatorial approaches of TCBs with other therapeutic strategies targeting T-cell dysfunction

A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1–) from non-small-cell lung cancer patients. PD-1T T cells showed a markedly different transcriptional and metabolic profile from PD-1N and PD-1– lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention