bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B076: PIN-2: A novel immunopriming peptide with immunomodulatory activity linking the innate and adaptive immune systems
Authors: Goldberg Joshua B. , Hanscom Sophie , Bier Colin B. 
Published: November 2016

Abstract
PIN-2 is a novel immunomodulatory agent derivatized from a transactivator protein. We have demonstrated its activity to both stimulate and induce maturation of monocytes into dendritic cells and translational proof of principle using an aggressive metastatic murine mammary cancer model.PIN-2 initiates activity by enhancement of innate immune signaling de novo. Next Generation Sequencing of CD14+ primary human monocytes after 3-hour exposure to PIN-2 in vitro, reveals a unique profile of gene expression indicative of innate immune activation which is necessary to drive adaptive immunity towards killer T-cell immune responses. Genetic programs in the monocyte impacted by PIN-2 exposure include cytokine signaling pathways, co-stimulatory ligands, and coding and non-coding RNAs.Understanding the genetic signature of the changes by PIN-2 through the innate immune response supports the rational development of immune based combination therapies such as cell based immunotherapies and checkpoint blockade that function to modulate adaptive immunity in T-cells in a clinical setting.
Citation Format: Joshua B. Goldberg, Sophie Hanscom, Colin B. Bier. PIN-2: A novel immunopriming peptide with immunomodulatory activity linking the innate and adaptive immune systems [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B076.
Abstract B080: Noninvasive imaging of antitumor responses as a possible predictive tool
Authors: Rashidian Mohammad , Ploegh Hidde 
Published: November 2016

Abstract
Immunotherapy has produced durable remissions across a spectrum of malignancies. However, predicting and monitoring therapeutic outcomes remains a challenge. Techniques to achieve these goals without multiple biopsies or other invasive methods will be critical to further improve on immunotherapy. Noninvasive imaging of immune responses is therefore a highly desirable goal. The abundance, movement and expansion of relevant cell types may yield reproducible patterns in responders and nonresponders that could help understand, if not predict, the failure or success of a therapy. To enable noninvasive imaging of the targeted cell populations, we isolated camelid-derived single domain antibody fragments (VHHs) against CD8, PD-L1, CTLA, Class II MHC, and CD11b markers. We also developed a method to site-specifically label VHHs with 18F, 64Cu or 89Zr. Radiolabeled VHHs rapidly clear the circulation (t1/2≈15-30 min) and clearly visualize their targets. Through PET imaging using radiolabeled VHHs, we can monitor and explore patterns of responses in the tumor microenvironment, as such or in response to therapy. Early results suggest that infiltration of a tumor by CD8 T cells may be used as a prognostic criterion. Tumors homogenously infiltrated by CD8-T cells appear more likely to respond than tumors that have heterogeneous CD8-T cell infiltration. Important next questions to be explored by PET imaging include the following. What is the role of regulatory T cells (Tregs) and macrophages? How does the CD8-T cell/Treg-cell ratio change in response to treatment? Is it possible to stratify responders from non-responders soon after starting therapy, and how would this affect treatment strategies? Because the basic methodology proposed here is in principle translatable to a human setting, this approach may ultimately find clinical application.
Citation Format: Mohammad Rashidian, Hidde Ploegh. Noninvasive imaging of antitumor responses as a possible predictive tool [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B080.
Abstract B089: High-throughput profiling of HLA allele-specific peptides by MS for improved epitope prediction
Authors: Rooney Michael S. , Abelin Jennifer G. , Keskin Derin B. , Sarkizova Siranush , Hartigan Christina , Zhang Wandi , Sidney John , Stevens Jonathan , Lane William J. , Zhang Guang L. , Clauser Karl R. , Hacohen Nir , Carr Steven A. , Wu Catherine J. 
Published: November 2016

Abstract
Cancer mutations yield neo-antigens, which are instrumental to immune-mediated recognition and control of cancer. Vaccine-based therapies targeting neo-antigens will require accurate prediction of which mutations yield peptides presented on polymorphic HLA class I. While in vitro methods have produced increasingly accurate predictors of peptide:MHC binding, there remains a need to define rules for endogenous antigen presentation. Here, we use rapid, high-resolution liquid chromatography mass spectrometry (LC-MS/MS) to identify &gt;24,000 peptides associated with 16 HLA alleles in B cell lines that each express a single HLA allele. The elution of peptides from single HLA alleles allowed us to develop improved rules for endogenous peptide presentation based on the physicochemical properties of binding peptides, patterns of peptide cleavage and abundance of cognate transcripts. Finally, we trained models that integrated MS-derived peptide data and gene expression and demonstrate improved prediction of endogenous peptide presentation in independent datasets. Our strategy thus improves the performance of current predictive algorithms and provides a rapid and scalable method to generate rules for the massive and diverse set of human HLA alleles.
Citation Format: Michael S. Rooney, Jennifer G. Abelin, Derin B. Keskin, Siranush Sarkizova, Christina Hartigan, Wandi Zhang, John Sidney, Jonathan Stevens, William J. Lane, Guang L. Zhang, Karl R. Clauser, Nir Hacohen, Steven A. Carr, Catherine J. Wu. High-throughput profiling of HLA allele-specific peptides by MS for improved epitope prediction [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B089.
Abstract B093: In vitro testing solid cancers immunotherapy protocols through impedance technology allows dynamic and label-free evaluation of immune response and reagent efficacy
Authors: Cerignoli Fabio , Xi Biao , Guenther Garret , Rector Trent , Muir Lincoln , Zhao Leyna , Abassi Yama 
Published: November 2016

Abstract
In vitro characterization of reagents efficacy in the context of cancer immunotherapy for solid tumors is a necessary step before moving to more expensive animal models and clinical studies. However, current in vitro assays are difficult to implement in high throughput environment and are mainly based on end point methodologies that are unable to capture the full dynamic of the immune response. Here we present the adaptation of an impedance-based platform to monitoring cytotoxic activity of immune cells activated trough different means. The technology detects cell death and proliferation of adherent cells by measuring changes in conductance of microelectrodes embedded in 96 and 384-wells cell culture plates. We utilized adherent cell lines and primary tumor cells with different expression levels of the EpCAM antigen, which is currently under evaluation as a target for cancer immunotherapy. Using PBMCs as effector cells and combinations of EpCAM/CD3 BiTE we demonstrated the suitability of such impedance-based approach to quantitatively monitor the efficacy of immune cells-mediated cancer cell killing both under different effector:target ratios and antibody concentrations. Combination treatments with checkpoint inhibitors were also effective when evaluated with the same approach. Finally, we validated the technology with engineered Car-T cells directed against common antigens expressed in tumors. Overall, our results demonstrate the value of such approach in measuring the cytotoxic response across the temporal scale, an aspect that is otherwise very difficult to assess with more canonical end point assays like Chromium 51 release or ATP-based luminescence. Furthermore, the availability of 384-wells format and minimal sample handling place the technology in an ideal spot for applications in personalized medicine, like therapeutic protocol validation directly on patient samples.
Citation Format: Fabio Cerignoli, Biao Xi, Garret Guenther, Trent Rector, Lincoln Muir, Leyna Zhao, Yama Abassi. In vitro testing solid cancers immunotherapy protocols through impedance technology allows dynamic and label-free evaluation of immune response and reagent efficacy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B093.
Abstract B096: Optogenetics-based dissection of chemotactic signaling in neutrophils
Authors: Graziano Brian R. , Gong Delquin , Anderson Karen E. , Weiner Orion D. 
Published: November 2016

Abstract
Neutrophils comprise a crucial component of the innate immune system and rely on chemotaxis (directed migration) to track down, engulf, and destroy pathogens. A variety of tumor-produced chemokines also recruit neutrophils to sites of tumor growth where, through mechanisms that remain unclear, they exhibit both beneficial and detrimental effects on tumor clearance. Effective chemotaxis requires that neutrophils restrict activity of the GTPase Rac to a single location to properly form a leading edge. However, multiple GEFs function redundantly to activate Rac and it has been difficult to determine where within the signaling cascade each specific GEF is required. Here, we develop an optogenetic tool to drive PIP3 production, which itself is sufficient to activate Rac in human neutrophil-like HL-60 cells. In cells where we used CRISPR-mediated editing to knockout the Rac GEF PREX1, we find that optogenetic stimulation of PIP3 production fails to activate Rac. In contrast, when these PREX1null neutrophils are instead treated with chemoattractant, other GEFs that do not explicitly rely on PIP3 production can still activate Rac. While signaling cascades often feature multiple redundant pathways functioning in parallel, our optogenetics-based approach reveals the location within such a network where a particular factor is necessary for the transmission of information. A more nuanced understanding of chemotactic signaling in neutrophils should lead to the development of treatments that can more precisely modulate the interactions between neutrophils and the tumor microenvironment.
Citation Format: Brian R. Graziano, Delquin Gong, Karen E. Anderson, Orion D. Weiner. Optogenetics-based dissection of chemotactic signaling in neutrophils [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B096.
Abstract B114: Innate immunity modulators to enhance oncolytic VSV-GP for the treatment of ovarian cancer
Authors: Kimpel Janine , Urbiola Carles R. , Dold Catherine , Marth Christian , Muik Alexander , Laer Dorothee Holm-von , Wollmann Guido 
Published: November 2016

Abstract
Oncolytic viruses (OV) that preferentially replicate in and kill tumor cells are promissing novel treatment option for advanced cancers. Through cell lysis, OV set tumor antigens free, which in combination with the OV adjuvant effect, unleashes a strong anti-tumor immune response. Here, we propose the use of the oncolytic VSV-GP for the treatment of ovarian cancer. Effective oncolytic activity of VSV-GP could be demonstrated in a panel of ovarian cancer cell lines. Analysis of the innate immune response of ovarian cancer cells to VSV-GP revealed IFN type I production and induction of an antiviral state of the cells as a potential mechanism leading to shortcomings in virotherapeutic treatment. In vivo, VSV-GP was tested in a subcutaneous ovarian cancer xenograft mouse model using the A2780 cell line. Treatment led to tumor remission, which was temporary in most mice resulting in tumor recurrance. In an orthotopic xenograft mouse model, intraperitoneal injection of the virus led to significantly prolonged survival compared to untreated animals. In addition, combination therapy of VSV-GP with the JAK1/2-inhibitor ruxolitinib was successfully tested in both models and found to enhance the oncolytic effect. The drug inhibited the signalling pathway induced by type I IFN and could thus be used to inhibit the antiviral innate immune response and enhance intratumoral viral replication. Importantly, despite inhibiting the antiviral response, no toxicity was observed in mice receiving up to 109 pfus (plaque forming units) VSV-GP via intraperitoneal application. In addition, using luciferase expressing VSV-GP, we found no off target tropism with ruxolitinib combination. In conclusion, VSV-GP was tested as a potent oncolytic virus to treat ovarian cancer. Restriction of viral replication due to the innate immune response could be overcome by the combination treatment of VSV-GP with the Jak-1/2 inhibitor ruxolitinib.
Citation Format: Janine Kimpel, Carles R. Urbiola, Catherine Dold, Christian Marth, Alexander Muik, Dorothee Holm-von Laer, Guido Wollmann. Innate immunity modulators to enhance oncolytic VSV-GP for the treatment of ovarian cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B114.
Abstract B133: Regulation of antiviral immune responses by RNase L
Authors: Clingan Jonathan , Eckard Sterling , Cooper Daphne , Ramos Hilario , Guillen Jaime , Canard Bruno , Gale Michael , Hesselberth Jay , Barton David , Stetson Daniel 
Published: November 2016

Abstract
Intracellular detection of RNA or DNA triggers distinct sensors that protect against virus infection: RNA activates the RIG-I-like Receptor (RLR)-MAVS pathway, whereas DNA activates the cyclic GMP-AMP Synthase (cGAS)-STING pathway. In addition, the oligoadenylate synthetases (OAS) detect foreign RNA and form 2'-5'-linked oligoadenylates (2-5A). The sole known function of 2-5A is to activate the endoribonuclease RNase L, which is thought to cleave cellular and viral RNAs indiscriminately into small fragments that activate the RLR response. We show here that, contrary to this prevailing view, RNase L-deficient cells have an enhanced antiviral response to RLR ligands. We find that the in vivo specificity of RNase L is restricted to ribosomal RNA and we establish RNase L as a specific regulator of protein translation, not an indiscriminate mediator of RNA decay. Our findings offer a revised view of the RNase L system, ascribing to it a negative regulatory role in the antiviral response and identifying rRNA as the primary target of RNase L activity.
Citation Format: Jonathan Clingan, Sterling Eckard, Daphne Cooper, Hilario Ramos, Jaime Guillen, Bruno Canard, Michael Gale, Jr., Jay Hesselberth, David Barton, Daniel Stetson. Regulation of antiviral immune responses by RNase L [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B133.
Abstract B142: Long non-coding RNA expression during CD8+ T cell differentiation and exhaustion
Authors: Hudson William , Kissick Haydn , Hashimoto Masao , Ahmed Rafi 
Published: November 2016

Abstract
Exhaustion of CD8+ T lymphocytes is a major barrier to effective clearance of chronic viral infection and cancer by the immune system. Transcriptional changes underlie the expansion and differentiation of a naive CD8+ T cell into various effector subsets, including the exhausted state. Experiments from other cell types have shown that the majority of the mammalian genome is transcribed, generating a large number of long, non-protein-coding RNAs (lncRNAs). These lncRNAs have been shown to play important roles in many cellular processes including histone modification, transcriptional regulation, and mRNA metabolism. To identify the role of lncRNAs in CD8+ T cell differentiation and exhaustion, we performed RNA-sequencing on functional and exhausted CD8+ T cells in both humans and mice. We identified over 1,000 expressed, previously un-annotated lncRNAs; of these, hundreds are differentially expressed over the course of CD8+ T cell differentiation. Exhausted CD8+ T cells express a unique set of lncRNAs, and this profile is altered with IL-2 treatment. These results suggest that lncRNAs play important roles in T cell differentiation and exhaustion, and further study is underway to determine their functional roles in anti-viral and anti-tumor immune responses.
Citation Format: William Hudson, Haydn Kissick, Masao Hashimoto, Rafi Ahmed. Long non-coding RNA expression during CD8+ T cell differentiation and exhaustion [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B142.
Abstract IA32: Visualizing tumor immune interaction in real time
Authors: Roberts Edward W. , Headley Mark B. , Broz Miranda , Boldjipour Bijan , Corbin Kaitlin , Binnewies Mikhail , Bins Adriaan , Gerard Audrey Audrey , Krummel Matthew 
Published: November 2016

Abstract
The nature of an immune response is rarely defined by a unanimous decisions by the participating cells; cells with seemingly opposing functions pervade many immune sites and tumors are no exception. Multiple DC and Macrophage subsets exert push/pull on T cell responses in tumors. Fundamentals of this are gleaned by live-imaging in connection with conventional methods such as flow-cytometry and immunofluorescence. Here, we broadly treat real-time imaging as a discovery tool to understand the tumor microenvironment (TME) and the diversity of cellular interactions that comprise host-tumor interactions. We have advanced this technology from sites of primary, spontaneous and aggressive tumors into sites of metastasis. The results promote the concept of seeking “allies” for tumor therapies within the TME and provide a basis for considering the balance of push/pull signals that determine the consensus immune response.
Citation Format: Edward W. Roberts, Mark B. Headley, Miranda Broz, Bijan Boldjipour, Kaitlin Corbin, Mikhail Binnewies, Adriaan Bins, Audrey Audrey Gerard, Matthew Krummel. Visualizing tumor immune interaction in real time [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA32.
Abstract PR03: HVEM (TNFRSF14) tumor suppressor in immune therapies of follicular lymphoma
Authors: Salloum Darin 
Published: November 2016

Abstract
Follicular lymphoma (FL) is among the most common and incurable forms of indolent B cell lymphoma. Somatic mutations that disrupt the HVEM (TNFRSF14) receptor gene in 28% of FL and include frequent homozygous lesions. The HVEM receptor interacts with the activating LIGHT and the inhibitory BTLA (B- and T- lymphocyte attenuator) receptors on B and T cells. Exactly, how HVEM mutations contribute to FL development is unknown. Here we show that the immune cell receptor HVEM (TNFRSF14) is a p53 response gene, and a frequent target of both somatic mutations, and recurrent chromosome 1p36 deletions in FL. Moreover, HVEM deficiency promotes FL development in vivo and establishes a favorable immune environment. Specifically, HVEM deficient lymphomas show an exaggerated activation of stromal components including follicular dendritic cells (FDCs) and increased recruitment of T follicular helper (TFH) cells that support B lymphocytes by secreting interleukins IL21 and IL4. Furthermore, HVEM loss stimulates B cell growth by disrupting an inhibitory BTLA (B and T Lymphocyte Attenuator) mediated signal. Notably, HVEM's tumor suppressor functions reside at the cell surface and extrinsic application of the HVEM ectodomain(P37-V202) can restore B cell growth control and block lymphoma growth in vivo. In addition, we demonstrate that CD19-specific, chimeric antigen receptor (CAR)-modified T cells that are further modified to constitutively secrete soluble HVEM ectodomain display significantly higher cytotoxicity against cancer B-cells with high BTLA expression in vivo.
Citation Format: Darin Salloum. HVEM (TNFRSF14) tumor suppressor in immune therapies of follicular lymphoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR03.
Poder demótico ao povo: o triunfo do <em>dimotiki</em>, o triunfo de Medeia
Authors: Bakogianni Anastasia 
Published: November 2016

Este texto analisa uma produção moderna da Medeia de Eurípides (431 a.C.) nos últimos anos do século passado. A releitura da tragédia antiga, que é objeto desta minha discussão, foi apresentada no Teatro Nacional da Grécia, em 1997, e dirigida por Niketi Kontouri. Representativa de um ambiente específico que, acredito, foi promovido no estado moderno grego depois da resolução oficial relativa à infame “Questão da Língua”, essa montagem também oferece uma perspectiva singular a partir da qual se pode reexaminar a Medeia de Eurípides e a recepção do drama grego no mundo moderno.
Socioeconomic Deprivation and Survival After Heart Transplantation in England
Authors: Evans Jonathan D.W. , Kaptoge Stephen , Caleyachetty Rishi , Di Angelantonio Emanuele , Lewis Clive , Parameshwar K. Jayan , Pettit Stephen J. 
Published: November 2016

Background—
Socioeconomic deprivation (SED) is associated with shorter survival across a range of cardiovascular and noncardiovascular diseases. The association of SED with survival after heart transplantation in England, where there is universal healthcare provision, is unknown.

Methods and Results—

Long-term follow-up data were obtained for all patients in England who underwent heart transplantation between 1995 and 2014. We used the United Kingdom Index of Multiple Deprivation (UK IMD), a neighborhood level measure of SED, to estimate the relative degree of deprivation for each recipient. Cox proportional hazard models were used to examine the association between SED and overall survival and conditional survival (dependant on survival at 1 year after transplantation) during follow-up. Models were stratified by transplant center and adjusted for donor and recipient age and sex, ethnicity, serum creatinine, diabetes mellitus, and heart failure cause. A total of 2384 patients underwent heart transplantation. There were 1101 deaths during 17 040 patient-year follow-up. Median overall survival was 12.6 years, and conditional survival was 15.6 years. Comparing the most deprived with the least deprived quintile, adjusted hazard ratios for all-cause mortality were 1.27 (1.04–1.55;
P
=0.021) and 1.59 (1.22–2.09;
P
=0.001) in the overall and conditional models, respectively. Median overall survival and conditional survival were 3.4 years shorter in the most deprived quintile than in the least deprived.

Conclusions—
Higher SED is associated with shorter survival in heart transplant recipients in England and should be considered when comparing outcomes between centers. Future research should seek to identify modifiable mediators of this association.