bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B062: Investigate the role of T lymphocytes in the regulation of energy expenditure and obesity
Authors: Hu Bo , Jin Chengcheng , Zeng Xing , Jedrychowski Mark , Zhao Chen , Banks Alex , Gigi Steven , Mathis Diane , Spiegelman Bruce 
Published: February 2019

Abstract
The increasing incidence of obesity and its co-morbid conditions poses a great challenge to global health. It is becoming clear that obesity is associated not only with type 2 diabetes mellitus and cardiovascular disease, but also with multiple types of cancer. Obesity and its associated inflammatory response has been closely linked to many aspects of cancer biology, including tumorigenesis, cancer immunotherapy and cancer cachexia. Obesity is caused by energy surplus when energy intake exceeds energy expenditure. As an important contributor of total energy expenditure is adaptive thermogenesis in brown adipose tissue, a promising and emerging avenue for obesity treatment is to increase energy expenditure by augmenting the activity of thermogenic adipocytes. Emerging evidence indicates that the immune system is instrumental in the control of host energy metabolism. However, the underlying mechanism has not been fully understood; specifically, the role of T-cells in regulating host thermogenesis has not been well studied. Here we identified that gamma delta T-cells and their associated signaling play a critical role in mediating adaptive thermogenesis in response to cold exposure in brown adipose tissue and high-fat-diet-induced obesity. In pursuing these studies we hope to discover new ways (targeting immune cells) to support the obesity treatment and reduce obesity-associated systemic inflammation and complications, especially cancer.
Citation Format: Bo Hu, Chengcheng Jin, Xing Zeng, Mark Jedrychowski, Chen Zhao, Alex Banks, Steven Gigi, Diane Mathis, Bruce Spiegelman. Investigate the role of T lymphocytes in the regulation of energy expenditure and obesity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B062.
Abstract B064: Chemical biology studies of anti-inflammatory lipids
Authors: Li Qiang , Hang Howard 
Published: February 2019

Abstract
A number of endogenous polyunsaturated fatty acids (PUFAs), including lipoxins, resolvins and protectins can help resolve inflammation and prevent various diseases. The beneficial effects in human health of these anti-inflammatory lipids have long been recognized, but their mechanism(s) of action and precise protein targets have remained unclear. Peroxisome proliferator-activated receptor γ (PPARγ) which is a ligand activated transcription factor and has been proposed to sense unsaturated and oxidized fatty acids may serve as a candidate target of these anti-inflammatory lipids. To address these questions, I have completed the total synthesis of anti-inflammatory lipid protectin D1 (PD1) by utilizing a convergent strategy. PPARγ-transactivation assay indicates that our synthetic PD1 potently activates PPARγ. I also evaluated the biochemical interactions of PD1 with PPARγ in cells using competitive photoaffinity labeling with a bifunctional fatty acid reporter (x-alk-16). Notably, over-expressed PPARγ can be crosslinked by x-alk-16 in a UV- and dose-dependent manner both in vitro and in mammalian cells. To further expand its application for endogenous PPARγ, I evaluated A549 cells and HT-29 cells, which also showed excellent x-alk-16 crosslinking of endogenous PPARγ both in vitro and in mammalian cells. These findings indicate that x-alk-16 can serve as a suitable photoaffinity fatty acid reporter to study PPARγ. By utilizing this chemical tool, the interaction of any bioactive small molecules with PPARγ can be evaluated. Several PPARγ synthetic ligands, including nTZDpa and rosiglitazone are chosen as a showcase for this study because they show very high affinity to PPARγ. These PPARγ synthetic ligands can compete the interaction between x-alk-16 and PPARγ. When applying PD1 as competitor, obvious competition effect can be observed, which suggests that PPARγ is one of the major protein targets of PD1. By performing unbiased chemical proteomic analysis, several unpredicted protein targets of PD1 were also identified and are currently being evaluated. Our findings should improve the current understanding of anti-inflammatory lipids targets and help elucidate the key pathways to improve the resolution of inflammation.
Citation Format: Qiang Li, Howard Hang. Chemical biology studies of anti-inflammatory lipids [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B064.
Abstract B066: Identifying novel effectors of the gut microbiota that modulate cancer cell killing by CTLs using functional metagenomics
Authors: Lobel Lior , Garrett Wendy S. 
Published: February 2019

Abstract
The immune system, which is profoundly affected by the microbiota composition and activity, plays an anti-tumorigenic role by surveying for and killing cancer cells. Indeed, recent studies found the microbiota to be essential for the success of cancer immunotherapy treatments in mice, while the bacterial effectors remain unknown. We developed an innovative high throughput screening system to isolate microbiota-derived effectors that modulate the ability of immune cells to kill cancer cells. We utilize the mouse CT26 colon carcinoma cell line as targeT-cells and the GSW11 specific CCD2Z T-cell hybridoma cell line as the effector cells. Bacterial DNA extracted from fecal contents of mice bearing colorectal tumors served for generation of metagenomics libraries. Supernatnants of the metagenomic clones were added to the CT26-CCD2Z co-culture and CCD2Z activation was measured using a LacZ reporter, regulated by NFAT. We identified about 40 clones that activate CCD2Z cells. We performed secondary screens and tested the activation of CD8+ T-cells sorted from mouse spleens. We sequenced the metagenomic DNA of several clones and analyzed the coding sequences. Currently, we are sub-cloning the clones to find the microbial genes responsible for CD8+ T-cell activation and design strategies for isolation of active molecules from these bacterial supernatnats. Finally, we hope that our future results could be taken to the clinic and serve for diagnosis, prognosis and therapeutics.
Citation Format: Lior Lobel, Wendy S. Garrett. Identifying novel effectors of the gut microbiota that modulate cancer cell killing by CTLs using functional metagenomics [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B066.
Abstract B070: Neoepitope and mutation load as a biomarker in a broad cohort of cancer patients treated with immunotherapy
Authors: Bjerregaard Anne-Mette , Lima Vinicius Araujo Barbosa de , Borch Annie , Oestrup Olga Araujo Barbosa de , Lassen Ulrik , Hadrup Sine Reker 
Published: February 2019

Abstract
Various different treatments of immunotherapy have in recent years made their mark in mainstream oncology, but it is still uncertain which patients will benefit and why. To determine this, different biomarkers have been investigated including tumor specific peptides originating from somatic mutations and recognized by T-cells, neoepitopes. Recent studies show that clinical benefit of immunotherapy correlate with both high mutational burden and high neoantigen load in defined patient groups, melanoma and lung cancer, underlining the possibility to use these measurements as biomarkers, and driving the hypothesis that neoantigen-responsive T-cells are the main drivers to cancer-cell elimination. We propose to investigate if a high mutational load and a high amount of neoepitopes are correlated with a general respond to immunotherapy across different cancer types and immunotherapy treatments. To examine this correlation, we studied 19 patients who have been treated with different kinds of immunotherapy. The data consist of Whole Exome Sequencing (WXS) data from blood and tumor, as well as tumor mRNA sequencing from all patients. Neoepitope load was predicted using Mutant peptide extractor and informer (MuPeXI) to find possible neoepitopes and score the neopeptides by their potential immunogenicity. The analysis of the sequencing data from the 19 patients revealed that even though these patients have cancers of varying origin and treated with different immunotherapies, a significant correlation was observed between a high number of neoepitopes as well as high mutational load with an increased possibility of a clinical benefit to immunotherapy. These findings showed that overall a clinical benefit is correlated with increased mutational load and neoepitopes independent of the cancer type and treatment which if used as a biomarker can possibly stratify patients determining who is likely to respond to cancer immunotherapy. Furthermore, we examined the tumor mRNA for T-cell recpetor sequences, and interestingly patients with high level of predeicted neoepitopes show enhanced oligoclonality of TCRs at the tumor site.
Citation Format: Anne-Mette Bjerregaard, Vinicius Araujo Barbosa de Lima, Annie Borch, Olga Araujo Barbosa de Oestrup, Ulrik Lassen, Sine Reker Hadrup. Neoepitope and mutation load as a biomarker in a broad cohort of cancer patients treated with immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B070.
Abstract B080: Improved neoantigen vaccine selection by combining prediction of pMHC presentation and T-cell epitopes
Authors: Kodysh Julia , O'Donnell Tim , Blazquez Ana B. , Finnigan John , Bhardwaj Nina , Rubinsteyn Alex 
Published: February 2019

Abstract
The OpenVax group has helped initiate two neoantigen vaccine clinical trials (NCT02721043, NCT02721043) at Mount Sinai based on a simple multiplicative ranking criterion which assigns equal weight to expression and predicted Class I MHC binding affinity of mutated peptides (1). This poster seeks to better ground our ranking method for selecting the contents of neoantigen vaccines in several sources of immunological data. We built a better model of MHC-I presentation on the cell surface by relating RNA expression and MHC affinity to pMHC ligands identified with mass spectrometry (2). Secondly, we trained a model of overall T-cell immunogenicity whose primary input is the predicted pMHC presentation score of any peptide-MHC combination, alongside other features such as similarity to the self proteome. This model is trained on T-cell response data deposited in the Immune Epitope Database (3). Lastly, we assembled a small dataset of peptide sequences used in neoantigen vaccine trials (1,4,5), which are labeled by whether they achieved a CD8+ or CD4+ T-cell response. This dataset allows us to explore several hypotheses about the relationship between immunogenic response and sequence similarity to both the self proteome and pathogenic proteomes. References: 1. Rubinsteyn A, Kodysh J, …, Hammerbacher J. Computational pipeline for the PGV-001 Neoantigen Vaccine Trial. Frontiers in Immunology 2018. 2. Abelin JG, Keskin DB,..., Wu CJ. Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction. Immunity 2017. 3. Vita R, Overton JA, …, Peters B. The immune epitope database (IEDB) 3.0. Nucleic Acids Res 2014. [4. Sahin U, Derhovanessian E, …, Türeci Ö. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 2017. 5. Ott P, Hu Z, …, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017.
Citation Format: Julia Kodysh, Tim O'Donnell, Ana B. Blazquez, John Finnigan, Nina Bhardwaj, Alex Rubinsteyn. Improved neoantigen vaccine selection by combining prediction of pMHC presentation and T-cell epitopes [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B080.
Abstract B103: Altering the mevalonate pathway to enhance CD8+ T-cell responses
Authors: Burn Olivia K. , Authier-Hall Astrid , Brooks Collin , Anderson Regan , Marshall Andrew , Painter Gavin , Weinkove Robert , Hermans Ian 
Published: February 2019

Abstract
Inhibitors of the mevalonate pathway have been found to induce inflammatory reactions and delay the progression of cancer. Emerging evidence suggests these inhibitors sensitise immune cells to signalling from the myeloid differentiation primary response gene 88 (MyD88) and in turn enhance NF-κB dependent activation of antigen presenting cells (APCs), an essential element in inducing an immune response. To further explore the adjuvant effect of these inhibitors, we designed a vaccine comprising an inhibitor of the mevalonate pathway conjugated to a tumor-specific peptide. We hypothesized that immunisation with these vaccines would elicit functional peptide-specific CD8+ T-cells. Using an in vivo mouse model, we found the vaccine generates greater peptide-specific cytotoxicity against targeT-cells bearing a human papillomavirus antigen than its unconjugated components, a chemical control vaccine or peptide alone. Moreover, the vaccine delayed outgrowth of an antigen-expressing tumor. Using human PBMCs, we obtained preliminary evidence that a similar vaccine can promote greater in vitro activation of CD8+ T-cells specific for a cytomegalovirus antigen than peptide alone. These results suggest that inhibitors of the mevalonate pathway can act as adjuvants in eliciting cytotoxic T-cell responses, and may have utility for the treatment or prevention of viral infections or neoplasia.
Citation Format: Olivia K. Burn, Astrid Authier-Hall, Collin Brooks, Regan Anderson, Andrew Marshall, Gavin Painter, Robert Weinkove, Ian Hermans. Altering the mevalonate pathway to enhance CD8+ T-cell responses [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B103.
Abstract B105: A cancer vaccine targeting many neoantigens is required for effective eradication of large tumors
Authors: D'Alise Anna Morena , Leoni Guido , Cotugno Gabriella , Troise Fulvia , Langone Francesca , Fichera Imma , Lucia Maria De , Vitale Rosa , Leuzzi Adriano , Bignone Veronica , Matteo Elena Di , Tucci Fabio Giovanni , Avalle Lidia , Poli Valeria , Lahm Armin , Catanese Maria Teresa , Folgori Antonella , Colloca Stefano , Nicosia Alfredo , Scarselli Elisa 
Published: February 2019

Abstract
Cancer neoantigens (nAgs) have the potential to elicit strong and tumor-specific immune responses and are, therefore, of great interest for cancer immunotherapeutic strategies, including therapeutic vaccines. Here we developed a novel neoantigen cancer vaccine based on adenoviruses derived from non-human Great Apes (GAds). GAds vaccination was highly effective in prophylactic or early therapeutic treatment of mouse tumors, independently of the number of encoded nAgs. In presence of high tumor burden, GAd has no antitumor effect unless combined with anti-PD1 treatment. In this more stringent setting, effectiveness of vaccination required the targeting of many neoantigens. Analysis of gene expression profile of tumors from responder mice showed greater diversification of the T cell repertoire with increased number of clonotypes in combo treated animals compared to anti-PD-1. Data suggest that GAd vaccines encoding a large number of nAgs can synergize with checkpoint inhibitors therapy by increasing the breadth of nAgs-specific T cells.
Citation Format: Anna Morena D'Alise, Guido Leoni, Gabriella Cotugno, Fulvia Troise, Francesca Langone, Imma Fichera, Maria De Lucia, Rosa Vitale, Adriano Leuzzi, Veronica Bignone, Elena Di Matteo, Fabio Giovanni Tucci, Lidia Avalle, Valeria Poli, Armin Lahm, Maria Teresa Catanese, Antonella Folgori, Stefano Colloca, Alfredo Nicosia, Elisa Scarselli. A cancer vaccine targeting many neoantigens is required for effective eradication of large tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B105.
Abstract B110: Proinflammatory allogeneic dendritic cells promote activation of bystander immune cells and indirectly license antigen-specific T-cells
Authors: Fotaki Grammatiki , Jin Chuan , Kerzeli Iliana Kyriaki , Ramachandran Mohanraj , Karlsson-Parra Alex , Yu Di , Essand Magnus 
Published: February 2019

Abstract
Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens have frequently been utilized as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidences indicate that such DCs are poor in migration and in fact do not directly interact with naïve T-cells in vivo. Instead, it is the bystander host-DCs taking up material from apoptotic vaccine DCs and subsequently initiate antitumor T-cell responses. We examine the possibility of harnessing allogeneic pro-inflammatory DCs (alloDCs) as immune enhancers which may affect the activation of bystander immune cells and promote antigen-specific T-cell responses. We have verified the inflammatory state of DCs matured with a maturation cocktail in combination with an infection-enhanced adenovirus. Such proinflammatory alloDCs expressed co-stimulatory and activation molecules and secreted Th-1 type cytokines in vitro. T and NK cells up-regulated activation markers after co-culture with such alloDCs and created an immunostimulatory environment which was found to promote maturation of antigen-loaded DCs and the subsequent activation of antigen-specific T-cells by cross-presentation. Our findings were evaluated as a therapeutic strategy in murine models with success. We are proposing that vaccination with proinflammatory alloDCs in combination with the use of Ad5M as possible antigen delivery vehicle can be a cost-effective strategy to induce antitumor immune responses.
Citation Format: Grammatiki Fotaki, Chuan Jin, Iliana Kyriaki Kerzeli, Mohanraj Ramachandran, Alex Karlsson-Parra, Di Yu, Magnus Essand. Proinflammatory allogeneic dendritic cells promote activation of bystander immune cells and indirectly license antigen-specific T-cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B110.
Abstract B112: Combined therapy with an autologous tumor cells/bacillus Calmette-Guérin/formalin-based vaccine plus anti-PD-1 inhibitor enhances the antitumor response in a 4T1 breast cancer model
Authors: Calderon Maria Jose Godoy , Marcano Eglys González , Convit Ana Federica 
Published: February 2019

Abstract
Immune checkpoint inhibitors have shown satisfactory results in different types of cancer, such as lung cancer and melanoma. However, in breast cancer their benefit as a stand-alone treatment have not been robust, suggesting the need of combined therapies. In preclinical and clinical studies some checkpoint inhibitors have shown enhancement of cancer vaccines’ antitumor effects. Cancer vaccines represent a promising immunotherapy since they induce a specific long-term immune response against tumor antigens, leading to an effective tumor elimination with minimal side effects. Based on successful previous experiences using an autologous tumor cells/bacillus Calmette-Guérin (BCG)/formalin-based vaccine in breast cancer, we aimed to enhance its antitumor properties by combining it with anti-PD-1. We used a 4T1 breast cancer model in BALB/c mice, receiving four weekly injections of either Phosphate Buffered Saline (G1), 50 μg anti-PD-1 (G2), or the vaccine plus anti-PD-1 (200 µg autologous tumor cells, 0.0625 mg BCG, 0.02% formalin plus 50 μg anti-PD-1) (G3). In G3, the tumor arrest ability of anti-PD-1 was enhanced, showing a stronger antitumor response compared to G2. This response was characterized by a high infiltration of CD8+ T and PD-1+ cells, and a likely prevalence of CD4+ Th1 cells as suggested by a low T CD4/CD8 ratio. This led to a marked tumor elimination represented by nearly 70% of tumor necrosis, and a 3-fold reduction of both tumor volume and mitotic index. Interestingly, anti-PD1 seemed to successfully enhance an important part of the vaccine’s antitumor response, indicated by 50% less TAMs infiltration and 10% more necrosis, though not significantly improving the overall antitumor effect of the vaccine. These limitations of the combined therapy may be overcome by using a higher anti-PD-1 dose and administering the two treatments at different times. Furthermore, the positive and promising effects of applying both treatments individually and combined, plus the vaccine’s low-cost and simple preparation method, encourage us to continue this study. The vaccine should be evaluated in combination with other checkpoint inhibitors and/or other target-specific compounds that can lead to new, highly effective, less toxic, personalized breast cancer immunotherapies.
Citation Format: Maria Jose Godoy Calderon, Eglys González Marcano, Ana Federica Convit. Combined therapy with an autologous tumor cells/bacillus Calmette-Guérin/formalin-based vaccine plus anti-PD-1 inhibitor enhances the antitumor response in a 4T1 breast cancer model [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B112.