From Self-fulfilment to Survival of the Fittest: Work in European Cinema from the 1960s to the Present, by Ewa Mazierska

In From Self-fulfilment to Survival of the Fittest: Work in European Cinema from the 1960s to the Present Ewa Mazierska aims to “gauge how much life is left in the distinguished ghost” of communism in Europe (3). Mazierska makes clear that her book is intended as a contribution to the recent attempts to revive Marxist thought in film and cultural studies—and, indeed, the monograph is one of several publications by the author through which she thoughtfully deploys Marxist thought in her analysis of European cinema. A theoretically sophisticated and highly readable study, at once a history of work on screen and a critique of capitalism (and latterly its neoliberal variant), the book is also intended to address the paucity of scholarly interest in the topic—a paucity that is surprising given that, as she argues, work is nearly always present on screen, whether actually represented or as a context for on-screen behaviour, character types, and relationships

Marginalized Subjects, Mainstream Objectives: Insights on Outsiders in Recent German Film

Nick Hodgin addresses a series of films collectively known as Ostwind, which was part-financed by the German public broadcast channel, ORB. He considers the producers’ claim that the films in question offer an accurate view of life in eastern Germany that distinguishes them from other media representations.The article places the films in the context of other representations of eastern Germany in the period since unification and summarizes the contrasting approaches, from popular comedies to sombre non-mainstream accounts. Having briefly outlined some of the themes raised in other films of the series, Hodgin examines in detail those films which focus on the region’s marginalized groups, particularly within youth culture, whether disenfranchised eastern European refugees or resentful neo-Nazi gangs.Hodgin concludes that, in considering the lives of eastern Germany’s increasingly diverse community without recourse to standard post-unification discourse, the films do indeed mark a shift in the mainstream representation of the east. While these groups have not been absent from filmic portrayals of the east, the tendency has been to depict them according to crude stereotypes. The directors of the Ostwind films, however, tend towards an approach that seeks both to normalize these individuals and to challenge the prevailing view of the east German community

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Marginalised subjects, mainstream objectives:insights on outsiders in contemporary German film

Nick Hodgin addresses a series of films collectively known as Ostwind, which was part-financed by the German public broadcast channel, ORB. He considers the producers’ claim that the films in question offer an accurate view of life in eastern Germany that distinguishes them from other media representations. The article places the films in the context of other representations of eastern Germany in the period since unification and summarizes the contrasting approaches, from popular comedies to sombre non-mainstream accounts. Having briefly outlined some of the themes raised in other films of the series, Hodgin examines in detail those films which focus on the region’s marginalized groups, particularly within youth culture, whether disenfranchised eastern European refugees or resentful neo-Nazi gangs. Hodgin concludes that, in considering the lives of eastern Germany’s increasingly diverse community without recourse to standard post-unification discourse, the films do indeed mark a shift in the mainstream representation of the east. While these groups have not been absent from filmic portrayals of the east, the tendency has been to depict them according to crude stereotypes. The directors of the Ostwind films, however, tend towards an approach that seeks both to normalize these individuals and to challenge the prevailing view of the east German community