bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B018: Landscape of natural HLA class I ligand peptides of cancer cells
Authors: Kikuchi Yasuhiro , Kanaseki Takayuki , Hongo Ayumi , Tokita Serina , Torigoe Toshihiko , Vitaly Kochin 
Published: February 2019

Abstract
HLA class I ligand repertoire on cancer cells directly influences immune surveillance system against cancer. We performed large-scale mass spectrometric profiling of the natural HLA-A*2402 ligand peptides and unveiled the landscape of natural HLA class I ligand peptides derived from various cancer cells including colon cancer cells (SW480, Colo320, HCT15) and lung cancer cells (LHK2, Sq-1). Known A24-binding anchors (Y/F at P2 and F/L/I at P9) were largely conserved among the ligands; however, a subset of peptides had an unusual anchor (K/R at the C-terminal P9 or P10), suggesting diverse usage of anchors in certain types of cancer cells. Moreover, a certain amino acid residue had significantly low frequency in the N-terminal flanking sequence, suggesting that it might inhibit processing of the peptides. Profiling of the natural HLA ligands of cancer cells revealed "neoantigen" peptides derived from mutated genome DNA and "aberrant antigen" peptides derived from long noncoding RNAs as well as "cancer-germ cell antigen" peptides. Among the natural HLA ligands derived from cancer cells, immunogenicity of the "neoantigen" peptide was the highest. The landscape clarified immunogenic peptide repertoire that might be suitable for cancer vaccine as well as as-yet-unknown rules for antigen processing.
Citation Format: Yasuhiro Kikuchi, Takayuki Kanaseki, Ayumi Hongo, Serina Tokita, Toshihiko Torigoe, Kochin Vitaly. Landscape of natural HLA class I ligand peptides of cancer 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 B018.
Abstract B024: Using single-cell paired sequencing to isolate cancer-specific T-cell receptors for cancer immunotherapy
Authors: Lech Karolina , Correia Lucia , Beckmann Max , Busz Maria , Collison Sean , Davis Sterenn , Mallini Paraskevi , Scaife Sarah , Dukes Joseph , Jakobsen Bent K. , Williams Luke , Teng Michelle 
Published: February 2019

Abstract
Immunocore’s ImmTAC™ (Immune Mobilising Monoclonal TCR Against Cancer) platform combines affinity-enhanced T-cell receptor (TCR)-based targeting with an anti-CD3 scFv effector function to activate a cytotoxic T-cell response against cancer cells. A key part to this process is the identification of tumour epitope specific TCRs from tumor antigen-reactive T-cells. Here, we describe an integrated in-house process leading to the isolation of TCRs specific for validated cancer epitopes, coupled with rapid identification of TCR chains from individual clones using single cell sequencing. The process involves first strand cDNA generation and universal amplification using SmartSeq2 chemistry, followed by targeted sequencing of the TCR alpha and beta chains using next-generation sequencing (NGS). We have also leveraged the 10x Genomics VDJ/5’ counting platform to label and pool multiple experimental clones for repertoire sequencing within a single run. Together with Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq), we can reliably assign each T-cell clone to its sample of origin paired with transcriptomic information of epitope specific T-cell populations, linking TCR sequences to their functional phenotype.
Citation Format: Karolina Lech, Lucia Correia, Max Beckmann, Maria Busz, Sean Collison, Sterenn Davis, Paraskevi Mallini, Sarah Scaife, Joseph Dukes, Bent K. Jakobsen, Luke Williams, Michelle Teng. Using single-cell paired sequencing to isolate cancer-specific T-cell receptors for cancer 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 B024.
Abstract B044: Engineering CAR NK cells for antigen-dependent autocrine expansion
Authors: Shemesh Avishai , Roybal Kole T. , Lanier Lewis L. 
Published: February 2019

Abstract
Given promising results with chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies attention has turned to whether CAR natural killer (NK) cells might have utility in cancer immunotherapy. NK cells are known to have potent cytolytic function and the ability to secrete interferons and cytokines, including GM-CSF and interferon-γ (IFNγ) upon stimulation. In pre-clinical models CAR NK cells have been shown to have efficacy and possibly some advantages over CAR T-cells. Several biotechs and pharmas are currently exploring this approach, but a major limitation of NK cells is their inability to produce autocrine growth factors to promote their own expansion and activation. In the context of CAR NK cell therapy, a major limitation is the inability of the infused CAR NK cells to expand in the absence of cytokine signals to initiate their proliferation and enhance their effector functions. IL-12 and IL-15 are essential for the clonal expansion of NK cells; however, recombinant IL-12 and IL-15 are quite toxic when administered systemically. Additionally, engineering NK cells to constitutively secrete IL-12 or IL-15 is not an attractive strategy as this may also result in off-target toxicity. Our goal is to engineer chimeric receptors with the intracellular signaling domains of IL-12 or IL-15 receptors fused to the extracellular domains of cytokine receptors. Consequently, self-secreted cytokines by activated NK cells or recognition of tumor cells will provide autocrine growth signal, permit NK clonal expansion and enhance NK effector functions.
Citation Format: Avishai Shemesh, Kole T. Roybal, Lewis L. Lanier. Engineering CAR NK cells for antigen-dependent autocrine expansion [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 B044.
Abstract B048: Proteomic approaches for the identification of druggable protein and epigenetic targets to complement melanoma immunotherapy
Authors: Tackett Alan 
Published: February 2019

Abstract
Introduction: Immune checkpoint inhibitors (ICIs) have shown encouraging success for treatment of melanoma; however, approximately half of patients with advanced melanoma have primary ICI resistance and sub-populations of initially responding patients develop secondary resistance. To help address this, our group has used quantitative proteomic workflows to identify druggable molecular pathways in these non-responders. Specifically, we are targeting the identification of protein pathways involved in regulation of gene transcription and chromatin modification as these are upstream events in cellular programming. Experimental Procedures: We have used cutting-edge proteomic workflows to identify proteins and histone post-translational modifications that are dysregulated in ICI nonresponsive patient melanoma. Proteins were isolated from FFPE patient melanomas and analyzed by high-resolution mass spectrometry with a Thermo Fusion Orbitrap mass spectrometer. Mass spectrometric data was searched for proteins and histone post-translational modifications dysregulated in ICI nonresponding melanomas. Pathway analysis provided for the identification of molecular pathways dysregulated in ICI nonresponders. New Data: We have published a smaller-scale version of this proteomic study comparing 4 responding and 4 nonresponding melanomas (Sci Reports 2017;7:807). In new data, we have increased the sample size of this comparison to provide increased power and significance. We have also expanding our quantitative proteomic analysis by incorporating the use of Thermo Tandem Mass Tagging with FFPE samples. Furthermore, we present new workflows using fresh melanoma tumors that provide for specific enrichment of melanoma cells from human tumors. Conclusions: We have identified protein and histone epigenetic pathways that are dysregulated in ICI nonresponsive patient melanomas. These molecular pathways could be prime targets for therapeutic development for increasing responsiveness to ICI therapy. Furthermore, we have extended our proteomic capabilities to the analysis of enriched populations of melanoma cells isolated from fresh human tumors, which will provide for cell type-specific proteomic studies.
Citation Format: Alan Tackett. Proteomic approaches for the identification of druggable protein and epigenetic targets to complement melanoma 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 B048.
Abstract B050: Identification of PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 treatment using human tumor explants
Authors: Thommen Daniela S. , Koelzer Viktor H. , Herzig Petra , Bruijn Marjolein de , Voabil Paula , Braber Marlous van den , Hummelink Karlijn , Monkhorst Kim , Mertz Kirsten D. , Zippelius Alfred , Haanen John B.A.G. , Schumacher Ton N.M. 
Published: February 2019

Abstract
Reinvigoration of tumor-specific T-cells by cancer immunotherapies, in particular PD-1/PD-L1 blocking agents, has greatly improved clinical outcome in multiple cancer types. Nevertheless, durable clinical benefit is currently limited to a small number of patients. To achieve a better understanding of the immunologic determinants of response to anti-PD-1 therapy, we assessed transcriptional and functional profiles of tumor-infiltrating lymphocyte (TIL) subsets from non-small cell lung cancer specimens. Thereby, we identified a transcriptionally distinct CD8 TIL pool with enriched capacity for tumor recognition. This TIL pool, termed PD-1T TILs, is characterized by bright PD-1 expression and constitutive CXCL13 secretion, which can mediate immune cell recruitment to tertiary lymphoid structures. Notably, the presence of PD-1T TILs correlates with response and survival in a small cohort of lung cancer patients treated with PD-1 blockade. To assess the role of PD-1T TILs and CXCL13 for response to PD-1 blockade in other cancer types, we developed a platform using human tumor explants to visualize immunologic responses to anti-PD-1 on a patient-specific level. Analysis of the cellular and soluble tumor microenvironment composition as well as of treatment-induced changes in tumor-infiltrating immune cells revealed immunologic responses to anti-PD-1 in 5 different cancer types. Of note, responding tumors in different tumor types were characterized by a clear enrichment in both PD-1T TILs and CXCL13 production. Collectively, our data reveal a distinct state of PD-1 bright lymphocytes that are enriched for tumor-reactivity in human cancer, making them an attractive proxy for the antitumor potential of the intratumoral T-cell pool. Furthermore, we established technology using human tumor explants to measure the immunologic response to T-cell checkpoint inhibition on a personalized basis. Finally, with this approach we identified PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 in multiple cancer types, opening potential new avenues for therapeutic intervention and improved patient selection.
Citation Format: Daniela S. Thommen, Viktor H. Koelzer, Petra Herzig, Marjolein de Bruijn, Paula Voabil, Marlous van den Braber, Karlijn Hummelink, Kim Monkhorst, Kirsten D. Mertz, Alfred Zippelius, John B.A.G. Haanen, Ton N.M. Schumacher. Identification of PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 treatment using human tumor explants [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 B050.
Abstract B055: Enhanced detection of T-cells targeting unique neoantigens and shared mutated oncogenes for personalized cancer immunotherapy
Authors: Yossef Rami , Tran Eric , Gros Alena , Deniger Drew , Cafri Gal , Rosenberg Steven A. 
Published: February 2019

Abstract
Adoptive cell transfer (ACT) of selected tumor-infiltrating lymphocytes (TILs) targeting neoantigens can mediate tumor regression in selected patients with metastatic epithelial cancer. However, effectively identifying and harnessing neoantigen-reactive T-cells for patient treatment remains a challenge and it is unknown whether current methods to detect neoantigen-reactive T-cells are missing potentially clinically relevant neoantigen reactivities. We thus investigated whether the detection of tumor-neoantigen reactive TILs in epithelial cancers could be enhanced by enriching T-cells that express PD-1 and/or T-cell activation markers (CD134, CD137) followed by microwell culturing at limiting dilution cell concentrations to avoid overgrowth of non-reactive T-cells. Using this approach, in six patients with metastatic epithelial cancer including stomach, colon pancreatic and ovarian cancers, this method led to the detection of CD4 and CD8 T-cells targeting 19 neoantigens compared to only eight neoantigens recognized using our standard TIL fragment screening approach. In two patients, no recognition of mutated peptides was observed using our conventional screen, while our high-throughput approach led to the identification of five neoantigen reactive-TCRs against five different mutations from one patient and a highly potent MHC-II-restricted KRASG12V reactive TCR from a second patient. In addition, in a metastatic tumor sample from a patient with serous ovarian cancer, we isolated three MHC class-II-restricted TCRs targeting the TP53G245S “hot-spot” mutation. In conclusion, this approach provides a highly sensitive and specific platform to isolate clinically relevant neoantigen-reactive T-cells or their TCRs for cancer treatment.
Citation Format: Rami Yossef, Eric Tran, Alena Gros, Drew Deniger, Gal Cafri, Steven A. Rosenberg. Enhanced detection of T-cells targeting unique neoantigens and shared mutated oncogenes for personalized cancer 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 B055.
Abstract B060: Commensal bacteria Bifidobacterium stimulates an antitumor response via cross-reactivity
Authors: Bessell Catherine Ami 
Published: February 2019

Abstract
While recent studies have shown an important role of the microbiome in modulating anti-tumor immune responses, its mechanism remains unclear. One proposed mechanism is due to cross-reactivity between antigens expressed in commensal bacteria and neoepitopes found in tumors. We have identified a cross-reactive antigen expressed in commensal bacteria Bifidobacterium (Bifido.) “SVYRYYGL” (henceforth called SVY) and show that it conveys a neoantigen-specific cross-reactivity to the classic neoantigen “SIY.” The SVY-specific response was analyzed through biophysical experiments and molecular dynamics simulations, which showed that the SVY peptide bound the H2-Kb MHC (Kb) with an altered peptide configuration leading to a cross-reactivity but at a lower overall affinity for the transgenic, SIY-specific 2C T-cell receptor (TCR). By T-cell expansion studies, commensal bacteria SVY-specific T-cells populations have a cross-reactive SIY specific T-cell response and those T-cell populations can recognize tumors expressing the “SIY” antigen. Mice lacking Bifido. have a decreased commensal bacteria specific T-cell response and an altered TCR repertoire compared to Bifido. colonized animals. Moreover, Bifido. colonization not only shapes the SVY commensal bacteria-specific T-cell repertoire but selects for clones that are represented in the SIY T-cell repertoire. Cross-reactive SVY-specific T-cells recognize tumors bearing SIY in vivo in an adoptive T-cell transfer model and a murine melanoma model. Animals treated with cross-reactive SVY-specific T-cells had decreased tumor growth and extended survival. Our work demonstrates that commensal bacteria can directly stimulate antitumor immune responses via T-cell cross-reactivity and provides a proof of principle for how bacterial antigens can shape the T-cell landscape.
Citation Format: Catherine Ami Bessell. Commensal bacteria Bifidobacterium stimulates an antitumor response via cross-reactivity [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 B060.
Abstract B067: Distinct necessity of mitochondrial complex I and III for regulatory T-cell function
Authors: Steinert Elizabeth M. , Weinberg Samuel E. , Chandel Navdeep S. 
Published: February 2019

Abstract
Regulatory T-cells (Treg cells) are major mediators of immunological homeostasis and tolerance, and their actions suppress responses to self-antigens that are aberrant as well as anti-tumor. Recent studies have demonstrated that, relative to other CD4+ T-cell subsets, Treg cells display increased mitochondrial metabolism and the Treg cell lineage-defining transcription factor, FOXP3, promotes respiration. However, it remains unknown whether Treg cells require the mitochondrial respiratory chain for their suppressive capacity, lineage stability, or survival. Our lab recently found that constitutive Treg cell-specific ablation of mitochondrial respiratory chain complex III but not complex I resulted in the development of a fatal inflammatory disease early in life. Treg cells lacking complex III survived and maintained proliferative capacity, but displayed a loss of suppressive function. We found that in adults, tamoxifen induced deletion of mitochondrial complex III or complex I from Treg cells impaired tumorigenesis. Surprisingly, only loss of complex III resulted in the development of fatal inflammatory disease. Because mitochondrial complex I inhibitors are being explored for cancer treatments, we are investigating the mechanism by which loss of complex I activity in Tregs prevents tumorigenesis.
Citation Format: Elizabeth M. Steinert, Samuel E. Weinberg, Navdeep S. Chandel. Distinct necessity of mitochondrial complex I and III for regulatory T-cell function [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 B067.
Abstract B068: Vitiligo and melanoma: The role of cutaneous human commensal bacteria in antimelanocyte immune responses
Authors: Vujkovic-Cvijin Ivan 
Published: February 2019

Abstract
Immunotherapies designed to bolster endogenous immune responses against tumors, in the form of checkpoint blockade, have vastly improved survival for a host of cancers. However, despite these novel approaches, metastatic melanoma remains associated with high mortality and rapid progression, and a subset of patients do not respond robustly to checkpoint blockade. Development of new methods to boost endogenous immune responses against melanoma thus constitutes a critical step toward the management of disease. Of note, initiating immune responses against nonmutated melanocyte-specific protein antigens has shown efficacy in augmenting immunotherapies. Vitiligo is an autoimmune disease characterized by immune-mediated destruction of melanocytes, though the etiology of this disease remains poorly understood. Skin-resident microbes have been recently demonstrated to exert a profound effect on immune processes of the skin, including those that are associated with vitiligo progression. Identifying skin-resident microbes that initiate or exacerbate antimelanocyte immune responses, as well as the precise pathways that mediate these processes, may provide a novel framework for the development of immunotherapies to augment antimelanoma immune responses. Thus, we have recruited a cohort of individuals with and without vitiligo and profiled their skin microbiomes at various body sites. We have found that vitiligo subjects harbor a skin microbiota that is unique from healthy subjects, and have isolated several vitiligo-associated bacteria. Notably, a previously uncultured Corynebacterium species appears in greater abundance on vitiligo subjects than on control subjects. The immunomodulatory potential of this novel bacterium will be explored in murine models developed by our laboratory, including an adapted mouse model of vitiligo. Interrogation of this host-microbiome relationship may thus lead to the identification of novel targets and pathways by which to treat vitiligo and augment melanoma immunotherapies.
Citation Format: Ivan Vujkovic-Cvijin. Vitiligo and melanoma: The role of cutaneous human commensal bacteria in antimelanocyte immune 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 B068.
Abstract B087: MHC class II on cancer cells—Role in response to BCG therapy of bladder cancer
Authors: Redelman-Sidi Gil , Glickman Michael , Binyamin Anna , Antonelli Anthony 
Published: February 2019

Abstract
BCG, a live mycobacterium also used worldwide as a vaccine against tuberculosis, is one of the first successful immunotherapies of cancer. Despite being in clinical use for the treatment of non-muscle-invasive bladder cancer (NMIBC) for 4 decades, the mechanism by which BCG activates the immune system to destroy cancer cells is poorly understood and there are no reliable methods to predict a patient’s response to BCG treatment. Current data suggest that the efficacy of BCG depends on initial attachment of BCG to bladder cancer cells leading to activation of an immune response that is T-cell dependent. It is not known whether bladder cancer cells have a direct role in activating T-cells. Using an orthotopic mouse model of BCG treatment of bladder cancer we show that: 1) BCG induces tumor-specific immunity; 2) CD4+ T-cells are the main requirement for BCG efficacy and for the tumor-specific immunity engendered by BCG therapy;3) bladder cancer cells can directly activate CD4+ T-cells; 4) the efficacy of BCG depends on MHC class II expression on the surface of bladder cancer cells. These data suggest that bladder cancer cells directly activate and drive a CD4+ T-cell dependent immune response that is required for the efficacy of BCG. Current work in the lab is focused on characterizing MHC class II expression on human NMIBC specimens and determining whether expression of MHC class II on bladder cancer cells predicts clinical outcomes after BCG therapy.
Citation Format: Gil Redelman-Sidi, Michael Glickman, Anna Binyamin, Anthony Antonelli. MHC class II on cancer cells—Role in response to BCG therapy of bladder cancer [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 B087.