bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A036: Somato-germinomics antigens are immunogenic cancer stem cell antigens
Authors: Torigoe Toshihiko , Hirohashi Yoshihiko , Tsukahara Tomohide , Kanaseki Takayuki , Nakatsugawa Munehide , Kubo Terufumi , Vitaly Kochin 
Published: November 2016

Abstract
Introduction and Purposes: Cancer stem-like cells (CSCs) are the subpopulation of cancer cells that have stem-like phenotypes and high capacity for tumor initiation. These cells have a huge impact in the field of cancer therapy since they are resistant to standard chemoradiotherapy and responsible for disease recurrence. We have isolated CSCs by sphere formation assay or side population assay, and analyzed the immunopathological properties of CSCs derived from human solid cancers.Results: We could identify several genes that were characteristic to CSCs. Remarkably, some of them were expressed exclusively in testicles among normal adult organs and involved in spermatogenesis. siRNA-mediated knockdown of these genes caused decreased sphere-forming capacity and in vivo tumorigenicity, indicating that they were involved in the tumor initiation capacity of CSCs. They were highly immunogenic since specific cytotoxic T-cells (CTLs) were efficiently induced from peripheral blood lymphocytes of healthy volunteers as well as cancer patients. The CTLs exerted specific cytotoxicity against CSCs. We named them “Somato-germinomics antigens” in terms of the functioning antigens shared between somatic cancer cells and germ cells.Conclusion: Our data suggest that CSCs might utilize the specific machinery of germ stem cells for their tumor initiation and express immunogenic antigens. However, CSCs preferentially express PD-L1 on the cell surface, therefore escaping from immune surveillance. Based on these findings, we propose an immunotherapeutic strategy targeting CSCs.
Citation Format: Toshihiko Torigoe, Yoshihiko Hirohashi, Tomohide Tsukahara, Takayuki Kanaseki, Munehide Nakatsugawa, Terufumi Kubo, Kochin Vitaly. Somato-germinomics antigens are immunogenic cancer stem cell antigens [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 A036.
Abstract A039: Accurate identification and prioritization of candidate neoantigens from cancer exome sequencing
Authors: White James , Simmons John , Angiuoli Sam , Sausen Mark , Jones Sian , Kann Lisa , Shukla Manish , Sevdali Maria , Velculescu Victor , Diaz Luis , Zhang Theresa 
Published: November 2016

Abstract
Somatic, nonsynonymous genetic alterations present in cancer can lead to the formation of novel protein sequences and thus production of immunogenic “non-self” neoantigens. Those neoantigens with sufficient expression will be processed and presented on MHC molecules, subsequently inducing a tumor-specific T cell response. Emerging data from clinical studies suggest that neoantigen load and composition is associated with the efficacy of some immunotherapies. As neoantigens play central a role in the cancer-immunity cycle, it is critical to identify the most potent immunogenic neoantigens effectively and accurately. Here we have leveraged highly accurate cancer whole exome (WES) analyses from FFPE tumor tissue with a state-of-the-art analysis protocol to identify and prioritize candidate neoantigens most likely to promote an immune response. ImmunoSelect-R utilizes somatic variants from WES to ensure detection of true somatic peptides and minimize false positives, and provides accurate HLA typing from whole exome sequencing data with &gt;99.9% sensitivity and specificity. When applied to a set of experimentally validated neoantigens, ImmunoSelect correctly classified 18 out of 19 as strong neoantigen candidates, suggesting a sensitivity of greater than 90%. Moreover, in a small set of 10 patients, ImmunoSelect consistently ranked experimentally validated neoantigens within top 20% of all neoantigen candidates derived from whole exome sequencing. In summary, ImmunoSelect is able to identify and prioritize candidate neoantigens from cancer exome sequencing results effectively and accurately, enabling personalized cancer vaccine development, adoptive T-cell transfer, and prediction of response to checkpoint inhibitors
Citation Format: James White, John Simmons, Sam Angiuoli, Mark Sausen, Sian Jones, Lisa Kann, Manish Shukla, Maria Sevdali, Victor Velculescu, Luis Diaz, Theresa Zhang. Accurate identification and prioritization of candidate neoantigens from cancer exome sequencing [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 A039.
Abstract A055: Systematic discovery of combinationimmunotherapy targets in vivo
Authors: Cartwright Adam N. , Tay Rong En , Wucherpfennig Kai W. 
Published: November 2016

Abstract
Immunotherapy has demonstrated remarkable responses in patients with metastatic tumors. Targeting the inhibitory CTLA-4 and PD-1 receptors expressed by T cells induces durable responses in a subset of cancer patients, including advanced melanoma. However, cancers, such as melanoma, remain largely resistant to many forms of immunotherapy, most likely due to exploitation of additional, and unidentified, negative feedback loops. It is widely appreciated that combination therapies will be required to extend the benefit of checkpoint blockade. Current approaches for discovery of combination therapies emphasize a 1 + 1 approach in which an active drug is tested in combination with an experimental agent. We hypothesize that many opportunities for synergistic combinations are missed with this strategy. We propose to develop a novel in vivo technique for discovery of combination therapies in the tumor microenvironment. Single-cell RNA-seq will be used to discover genes upregulated in dysfunctional T cells during PD-1 or CTLA-4 monotherapy in a mouse model of melanoma. We will then screen a library of identified targets in CD8 T cells for synergistic combinations using checkpoint blockade along with CRSIPR/Cas9 genome editing. Enrichment within the tumor of specific targets will then be further investigated to determine the most efficacious combinations for the treatment of melanoma.
Citation Format: Adam N. Cartwright, Rong En Tay, Kai W. Wucherpfennig. Systematic discovery of combinationimmunotherapy targets in vivo [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 A055.
Abstract A057: CX3CR1 distinguishes three distinct migratory memory CD8 T cell subsets
Authors: Gerlach Carmen , Moseman E. Ashley , Loughhead Scott M. , Alvarez David , Zwijnenburg Anthonie J. , Waanders Lisette , Garg Rohit , Torre Juan C. de la , Andrian Ulrich H. von 
Published: November 2016

Abstract
CD8 T cells are crucial for the protection against tumors and intracellular pathogens via their ability to generate long-term memory. Memory T cells (TMem) are however not a homogenous population. Traditionally, blood-borne TMem have been sub-divided into central memory (TCM) and effector memory (TEM) cells based on different migration behaviors and cytotoxic potential.
We recently discovered the existence of a novel subset of CD8 TMem that has unique migratory properties and a superior homeostatic self-renewal capacity. The hitherto unrecognized memory CD8 T cell subset is characterized by intermediate expression levels of CX3CR1, while classical TCM were CX3CR1−, and TEM were CX3CR1high. The fraction of CX3CR1int cells among antigen-experienced TMem was remarkably stable over the course of a year, while TEM gradually declined and TCM increased to be the largest subset by 10 months. Interestingly, CX3CR1int TMem had the highest proliferation rate of the three TMem subsets. While TCM and TEM were phenotypically stable over &gt;10 weeks at steady state, CX3CR1int TMem not only self-renewed, but also gave rise to bonafide TCM. Consequently, CX3CR1int TMem contributed to the gradual increase in TCM.
The newly identified CX3CR1int TMem displayed unique migratory properties. Unlike CX3CR1high TEM, CX3CR1int gradually acquired lymph node homing capability. Moreover, parabiosis experiments and analysis of recirculating memory cells in thoracic duct lymph revealed that CX3CR1int TMem, not TEM, are the predominant T cell subset surveying non-lymphoid peripheral tissues.
Supported by a postdoctoral fellowship of the Cancer Research Institute Irvington Fellowship Program and a Rubicon fellowship (Netherlands Organization for Scientific Research, NWO) to CG, NIH T32 Training Grant in Hematology 5T32-HL07623-20 to EAM, NIH F31 grant CA171339 to SML, NIH T32 grant HL066987 to DA, the Ragon Institute of MGH, MIT and Harvard and NIH/NIAID RO1 AI069259, PO1 AI078897 and PO1 AI112521 to UHvA.
Citation Format: Carmen Gerlach, E. Ashley Moseman, Scott M. Loughhead, David Alvarez, Anthonie J. Zwijnenburg, Lisette Waanders, Rohit Garg, Juan C. de la Torre, Ulrich H. von Andrian. CX3CR1 distinguishes three distinct migratory memory CD8 T cell subsets [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 A057.
Abstract A058: Selective targeting of T regulatory cells by a TCR-mimic monoclonal antibody specific for foxp3-derived epitopes
Authors: Dao Tao , Jarvis Casey , Scott Andrew C. , Korontsvit Tatyana , Zakhaleva Victoria , Pankov Dmitry , Guerrerio Manuel Direito de Morais , Mathias Melissa , Cheng Neal , Liu Cheng , Scheinberg David A. 
Published: November 2016

Abstract
Immunosuppression by tumor-induced regulatory T (Treg) cells present major obstacles for successful immunotherapy. Treg expansion and its negative prognostic impact represent a general phenomenon seen in multiple types of cancer. Therefore, developing strategies for Treg depletion could enhance the reactivation of immune responses against the malignant tumor cells. However, the strategies of depleting Tregs have been hindered by the lack of specificity, which also leads to the depletion of anti-tumor effector cells. The transcription factor forkhead box p3 (FoxP3) is selectively expressed in and is essential to the suppressive function of Treg cells. FoxP3 thus would be an appealing target for eliminating Treg cells. However, Foxp3 is an undruggable intracellular protein. Here, we took a novel and unconventional approach to target Foxp3 by using a T cell receptor mimic (TCRm) mAb, which recognizes a human Foxp3-derived CD8 T cell epitope, presented by HLA-A*02:01 molecule. We show that the Foxp3 mAb specifically bound to CD4+CD25hiCD127lo Foxp3+ Treg cells from HLA-A0201 positive donors, and tumor cell lines co-expressing Foxp3 and HLA-A*02;01 molecule. Both afucosylated Fc enhanced human IgG1 and bispecific T cell engager formats of the Foxp3 mAb are able to kill in vitro-generated Treg clones from HLA-A0201+ donors and “Treg-like” cutaneous lymphoma cells (HLA-A*02:01+) that have a high level expression of CD4, CD25 and Fox3+. FoxP3-targeting antibodies could potentially be a novel approach in cancer immunotherapy by overcoming immunosuppression caused by Tregs and tumor cells expressing Foxp3.
Citation Format: Tao Dao, Casey Jarvis, Andrew C. Scott, Tatyana Korontsvit, Victoria Zakhaleva, Dmitry Pankov, Manuel Direito de Morais Guerrerio, Melissa Mathias, Neal Cheng, Cheng Liu, David A. Scheinberg. Selective targeting of T regulatory cells by a TCR-mimic monoclonal antibody specific for foxp3-derived epitopes [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 A058.
Abstract A063: Dissecting adipose tissue Treg differentiation and function in metabolism and obesity-associated cancer using TCR transgenic mice
Authors: Li Chaoran , Benoist Christophe , Mathis Diane 
Published: November 2016

Abstract
Recent epidemiological and animal model studies indicate that overweight and obese individuals have increased risk not only of type-2 diabetes and cardiovascular diseases but also of various types of cancer. It was suggested that chronic, low-grade inflammation of the adipose tissue, and eventually systemically, is one of the major causes for obesity-associated metabolic abnormalities and cancer, but the trigger, progression and regulation of obesity-induced inflammation and how these processes might influence the development of cancer remain poorly understood. Our laboratory previously discovered a unique population of Foxp3+ CD4+ regulatory T cells (Tregs), with a distinct transcriptome and clonally expanded T cell receptor (TCR) repertoire, residing in the visceral adipose tissue (VAT) of mice and humans. These cells are critical for regulating local inflammation and maintaining systemic insulin sensitivity, but whether they regulate the development of obesity- associated cancers is currently unknown. Moreover, we are still at the early stages of an integrative understanding of the differentiation, trafficking, and expansion of this unique population of VAT cells. Attempting to fill some of these knowledge-gaps, we developed a VAT Treg TCR transgenic (Tg) mouse line, in which Tregs preferentially accumulate in VAT upon recognition of a currently unknown antigen. With this unique tool, we elucidated the life history of VAT Tregs, determined when and where they accumulate and acquired the unique phenotype, identified factors that are important for their homeostasis, and demonstrated their function in suppressing insulin resistance. We are currently in the process of elucidating their function in controlling the obesity- promoted liver inflammation and tumorigenesis. This study will provide foundations for Treg-based immunotherapy against the metabolic syndrome and obesity-associated cancer, while pointing to new cellular and molecular pathways that may constitute potential therapeutic targets.
Citation Format: Chaoran Li, Christophe Benoist, Diane Mathis. Dissecting adipose tissue Treg differentiation and function in metabolism and obesity-associated cancer using TCR transgenic mice [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 A063.
Abstract A066: NF-kB restricts inflammasome activation via elimination of damaged mitochondria
Authors: Zhong Zhenyu , Karin Michael 
Published: November 2016

Abstract
NF-κB, a key activator of inflammation primes the NLRP3-inflammasome for activation by inducing pro-IL-1β and NLRP3 expression. NF-κB, however, also prevents excessive inflammation and restrains NLRP3-inflammasome activation through a poorly defined mechanism. We now show that NF-κB exerts its anti-inflammatory activity by inducing delayed accumulation of the autophagy receptor p62/SQSTM1. External NLRP3-activating stimuli trigger a form of mitochondrial (mt) damage that is caspase-1- and NLRP3-independent and causes release of direct NLRP3-inflammasome activators, including mtDNA and mtROS. Damaged mitochondria undergo Parkin-dependent ubiquitin conjugation and are specifically recognized by p62, which induces their mitophagic clearance. Macrophage-specific p62 ablation causes pronounced accumulation of damaged mitochondria and excessive IL-1β-dependent inflammation and enhances macrophage death. Therefore, the “NF-κB-p62-mitophagy” pathway is a macrophage-intrinsic regulatory loop through which NF-κB restrains its own inflammation-promoting activity and orchestrates a self-limiting host response that maintains homeostasis and favors tissue repair.
Citation Format: Zhenyu Zhong, Michael Karin. NF-kB restricts inflammasome activation via elimination of damaged mitochondria [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 A066.
Abstract A072: Glucose metabolism and O-linked GlcNAcylation in the tissue repair function of Treg cells
Authors: Hu Wei , Arpaia Nicholas , Green Jesse A. , Hendrickson Ronald C. , Rudensky Alexander Y. 
Published: November 2016

Abstract
Regulatory T (Treg) cells dampen immune responses to avoid excessive, deleterious inflammation in the context of autoimmunity, allergy, and infection. Treg cells also impede anti-tumor immunity. Therefore, modulation of Treg cell activity is of great therapeutic potential for treating many debilitating inflammatory diseases and cancer. Recent studies have suggested that in addition to their prominent immunosuppressive function, Treg cells have a distinct and non-redundant role in tissue maintenance and remodeling. These Treg cells exhibit a unique transcriptional signature represented by high expression of the EGF family member amphiregulin (Areg). Importantly, tumor infiltrating Treg cells highly express Areg. Since Areg is known to exert pleiotropic oncogenic activities, Areg producing Treg cells may be crucial for establishing the tumor microenvironment. It has been increasingly appreciated that lymphocyte activation and differentiation are coupled to specific metabolic pathways. Metabolic reprogramming is dictated by cytokine and growth factor signals, as well as the availability of nutrients. In addition, metabolic products provide substrates that can alter the functional status of a cell through posttranslational modifications (PTMs). Among the various nutrients, glucose is a key metabolic substrate for T cells. Aerobic glycolysis in activated T cells is required for the acquisition of full effector function. Treg cells in the secondary lymphoid organs and the tissue have distinct glucose availability and metabolic needs. We thus hypothesized that glucose sensing and glucose metabolism play essential roles in shaping the unique phenotype and function of tissue resident Treg cells. O-linked GlcNAcylation is a PTM dynamically regulated by glucose levels and controls the function of many proteins, including transcription factors that play key roles in T cell activation such as NF-κB, CREB, and NFAT. To understand the mechanism by which glucose metabolism controls the function of tissue-resident Treg cells, we began to characterize protein O-GlcNAcylation in Treg cells, and found that both human and mouse Foxp3, the master regulator transcription factor of Treg cells, undergoes O-GlcNAcylation. We are in the process of mapping the site of O-GlcNAcylation of Foxp3, and understanding the physiological significance of this PTM.
Citation Format: Wei Hu, Nicholas Arpaia, Jesse A. Green, Ronald C. Hendrickson, Alexander Y. Rudensky. Glucose metabolism and O-linked GlcNAcylation in the tissue repair function of Treg cells [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 A072.
Abstract A077: Identifying novel effectors of the gut microbiota that modulate cancer cell killing by CTLs using functional metagenomics
Authors: Lobel Lior , Garret Wendy 
Published: November 2016

Abstract
The immune system, which has close interactions with the microbiota, plays an anti-tumorigenic role by surveying for and killing cancer cells. In this regard, recent studies found the microbiota to be essential for the success of cancer immunotherapy treatments in mice, while the bacterial effectors remain unknown. We propose 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. Cytotoxicity and T cell activation assays, measured by LDH release and LacZ expression, respectively, were calibrated to both positive and negative controls and in response to an array of perturbations. Bacterial DNA from mouse colon tumors will serve for the generation of metagenomics libraries. We then plan to screen ∼ 30,000 clones and characterize the cellular and immune responses of identified effectors both in tissue cultures and in animals. 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 Garret. Identifying novel effectors of the gut microbiota that modulate cancer cell killing by CTLs using functional metagenomics [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 A077.
Abstract A080: Balance of commensal bacteria specific Th17 and RORγt+ Treg cells in intestinal homeostasis and inflammation
Authors: Xu Mo , Yang Yi , Pokrovskii Maria , Galan Carolina , Littman Dan R. 
Published: November 2016

Abstract
A number of Helicobacter species, including Helicobacter hepaticus, have been isolated as the etiological agents of ulcerative inflammatory bowel disease and cancer in their respective hosts. H. hepaticus induces severe Th17-Th1 mediated colitis in a number of immuno-compromised mouse strains, but does not usually cause disease in most wild-type mouse strains. However, how the inflammatory response is carefully contained to be harmless under homeostatic conditions and how perturbations lead to pathogenicity remain elusive questions. To understand this, we developed new research tools, including TCR transgenic mice, as well as MHCII tetramers to interrogate the regulation of H. hepaticus-specific CD4+ T cell function. Interestingly, in contrast to Segmented Filamentous Bacteria (SFB), which induces Th17 cells in the small intestinal lamina propria (SILP) of both IL10+/− and IL-10−/− mice, H. hepaticus mainly induces RORgt+ Treg cells in the large intestinal lamina propria (LILP) of IL-10-sufficient mice, but induces a Th17-Th1 response in the absence of IL-10. We propose that the balance between self/commensal antigen-induced RORgt+ Treg and Th17 cells may be a general strategy to control autoimmune inflammation.
Note: This abstract was not presented at the conference.
Citation Format: Mo Xu, Yi Yang, Maria Pokrovskii, Carolina Galan, Dan R. Littman. Balance of commensal bacteria specific Th17 and RORγt+ Treg cells in intestinal homeostasis and inflammation [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 A080.