bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract TS1-1: Advanced enabling technologies for cancer proteomics
Authors: Liu T 
Published: March 2020

Abstract
Mass spectrometry-based proteomics is a promising technology in characterization of human proteome at a genome scale, facilitating proteogenomic characterization of cancer specimens. Recent advances in mass spectrometry instrumentation, sample handling platforms, and proteomic analysis strategies allow for not only large-scale, comprehensive proteome profiling, but also focused systems biology studies, biomarker verification, as well as analysis of protein expression and phosphorylation in very small populations of cells. This will lead to significantly improved understanding of aberrant regulatory and signal transduction networks underlying cancer for translational applications.
Citation Format: T Liu. Advanced enabling technologies for cancer proteomics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr TS1-1.
Abstract TS2-1: CTC Clusters, Cancer Stemness, and New Treatment Strategies
Authors: Liu H 
Published: March 2020

Abstract
Circulating tumor cells (CTCs) seed metastases which eventually kill most of the breast cancer patients; however, CTCs have not been effectively targeted partially due to the unclear cellular and molecular mechanisms. Emerging evidence and our studies demonstrate that CTCs are detectable as singles as well as multicellular clusters in cancer patients; and presence of the latter is associated with unfavorable progression-free survival (PFS) and poor overall survival (OS). Compared to single CTCs, CTC clusters show enriched stemness properties, including enhanced tumorigenic potential and polyclonal metastases, more efficient mammosphere formation, and upregulated expression of CD44 and stemness-related signaling pathways. Using intravital multiphoton microscopic imaging of patient-derived-xenograft (PDX) models and mouse tumor models, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding. Molecularly, the intercellular CD44-CD44 homophilic interactions are essential for the multicellular CTC aggregation, recruitment of downstream PAK2, and activation of the FAK signaling. Depletion of CD44 or antibody-mediated blockade of CD44 interactions effectively prevent tumor cell aggregation and abolish polyclonal metastases. In addition to CD44, we have identified other surface receptors and adhesion molecules which also contribute to CTC cluster formation. Our studies highlight that CTC clusters, whose presence is correlated with a poor prognosis of breast cancer patients, can serve as a liquid biopsy-based biomarker as well as novel therapeutic targets of polyclonal metastasis.
Citation Format: H Liu. CTC Clusters, Cancer Stemness, and New Treatment Strategies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr TS2-1.
Abstract TS2-2: Biology, Vulnerabilities and Clinical Implications of CTC Clusters
Authors: Aceto N 
Published: March 2020

Abstract
CTC clusters have recently emerged as key players in the metastatic process. With a combination of microfluidic technologies and single cell-resolution molecular analysis applied to breast cancer patients and mouse models, we gained fundamental insights into the biology, vulnerabilities, and clinical implications of CTC clusters. For instance, we found that their physical features enable molecular changes that promote stemness and metastasis, allowing us to define new treatments to suppress their metastatic potential. Further, we investigated CTC heterogeneity at the single cell level, revealing fundamental interactions that occur between CTCs and immune cells and that accelerate metastasis formation. Thus, our findings support a model whereby CTCs form multicellular aggregates with each other as well as with immune cells to expand their metastatic potential, providing a new rationale for targeting these interactions in breast cancer.
Citation Format: N Aceto. Biology, Vulnerabilities and Clinical Implications of CTC Clusters [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr TS2-2.
NF-κB–Activated miR-574 Promotes Multiple Malignant and Metastatic Phenotypes by Targeting BNIP3 in Thyroid Carcinoma
Authors: Zhang Zhe-Jia , Xiao Qian , Li Xin-Ying 
Published: March 2020

Abstract

Thyroid cancer is the most common endocrine malignancy, and miR-574 is significantly upregulated in thyroid cancer. However, the role and underlying mechanism of miR-574 in thyroid cancer development are poorly understood. In this study, we showed that NF-κB/p65 signaling pathway was activated and miR-574 was upregulated in thyroid cancer cells. p65 directly bound to the promoter of miR-574 and activated miR-574 transcription. Functionally, miR-574 inhibited apoptosis, promoted proliferation and migration of thyroid cancer cells, and stimulated thyroid cancer–induced tube formation of endothelial cells. On the molecular level, miR-574 inhibited the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) by binding to 3′-UTR of BNIP3. miR-574 also downregulated the expression of apoptosis-inducing factor (AIF), while elevated the levels of MMP2, MMP9, and VEGFA. In vivo, miR-574 promoted xenograft growth, which was associated with reduced apoptosis and enhanced angiogenesis. NF-κB/miR-574 signaling presents multiple oncogenic activities on thyroid cancer development by directly regulating the BNIP3/AIF pathway. Therefore, targeting NF-κB/miR-574 signaling may reduce the aggressiveness of thyroid cancer.

Implications:
miR-574, directly regulated by NF-κB/p65, promotes tumorigenesis of thyroid cancer via inhibiting BNIP3/AIF pathway.
Abstract A100: Downregulation of type 1 interferon receptor (IFNAR1) regulates the balance of regulatory T cells (Tregs) and cytotoxic T lymphocytes (CTLs) in tumor microenvironment
Authors: Zhang Hongru , Gui Jun , Ortiz Angelica , Fuchs Serge 
Published: March 2020

Abstract
Solid tumors are infiltrated by not only CD8+ effector T cells (CTLs) exerting tumoricidal function, but also by regulatory T cells (Tregs), which are a key barrier to antitumor immunity (1). In the tumor microenvironment, the type 1 interferon (IFN) signaling is downregulated due to proteolytic degradation of IFNAR1 (2). Reduced IFNAR1 levels in tumor stroma are important for establishing the immune privileged niche to support tumor development and progression (3). IFN pathway plays complex and controversial roles in regulating immune responses ([4-7). In this study, we show that loss of IFNAR1 leads to changes in the activities of Tregs and CTLs. Genetic stabilization of IFNAR1 (Ifnar1S526A, SA) recruits more CTLs in the tumor microenvironment; however, it does not change the frequency of Tregs. In addition, in SA tumor tissues, the CTLs appear to exhibit a greater tumoricidal activity. Furthermore, we find that SA Treg lost their inhibitory function and SA CTLs are resistant to Treg-mediated immune suppression. In all, we discuss putative mechanisms underlying these phenotypes that IFN pathway regulates the balance of Treg and CTL activities in the tumor microenvironment.
Citation Format: Hongru Zhang, Jun Gui, Angelica Ortiz, Serge Fuchs. Downregulation of type 1 interferon receptor (IFNAR1) regulates the balance of regulatory T cells (Tregs) and cytotoxic T lymphocytes (CTLs) in tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A100.
Abstract A107: Microfluidics and oncoimmunology: New in vitro models to study solid tumor immunotherapy
Authors: Ayuso Jose M. , Virumbrales-Munoz Maria , McMinn Patrick H. , Rehman Shujah , Fitzgerald Cate M. , Beebe David J. , Skala Melissa C. 
Published: March 2020

Abstract
Immunotherapies against solid tumors face daunting challenges compared with hematologic cancers. In solid tumors, immune cells and antibodies need to extravasate from the vasculature, find the tumor cells, and migrate through a dense mass of normal and tumor cells where nutrients are depleted and waste products build up. All these factors pose significant obstacles for solid tumor immunotherapy, commonly leading to immune exhaustion and compromising the immune response. Thus, finding effective immunotherapies against solid tumors requires in vitro models that accurately capture the tumor complexity. In this work, we present microfluidic models for solid tumor immunotherapy and show how they mimic the tumor architecture in an unprecedented way compared with other traditional in vitro models based on Petri dishes. Breast cancer cells were cultured as a dense mass and embedded in a 3D collagen hydrogel into a microfluidic device. Endothelial cells were cultured in lateral flanking lumens to mimic the blood vessels, allowing the perfusion of therapeutic antibodies or effector immune cells (e.g., natural killer cells). Antibody and immune cell extravasation, diffusion, migration, and tumor clearance were evaluated in the model, showing the NK cell capacity to detect the presence of the tumor hundreds of microns away. Once inside the tumor mass, real-time microscopy revealed natural killer cells were able to destroy tumor cells at the tumor periphery and, more importantly, also at the innermost layers. The combination of antibodies and natural killer cells led to an enhanced cytotoxicity, showing the potential of the model to evaluate new immunotherapy combinations. Finally, tumor, endothelial, and NK cells were retrieved at different locations of the tumor (e.g., tumor margin vs. tumor core) and at different time points to show how these different cell populations adapted to the continuously evolving tumor microenvironment.
Citation Format: Jose M. Ayuso, Maria Virumbrales-Munoz, Patrick H. McMinn, Shujah Rehman, Cate M. Fitzgerald, David J. Beebe, Melissa C. Skala. Microfluidics and oncoimmunology: New in vitro models to study solid tumor immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A107.
Abstract A14: Neoepitope-specific CD8+ T cells in adoptive T-cell transfer
Authors: Kristensen Nikolaj Pagh , Heeke Christina , Tvingsholm Siri A. , Bjerregaard Anne-Mette , Draghi Arianna , Bentzen Amalie Kai , Andersen Rikke , Donia Marco , Svane Inge Marie , Hadrup Sine Reker 
Published: March 2020

Abstract
Adoptive T-cell therapy (ACT) relies on expansion of tumor-infiltrating lymphocytes and infusion into patients following lymphodepletion, which have yielded complete responders in up to 25% of treated patients suffering from metastatic melanoma. However, a large proportion of patients have no clinical benefit (50-60%). Previous studies have found that clinical outcome correlates with tumor mutational and putative neoantigen load. Furthermore, expression of core antigen-presentation pathways including MHC class I genes in tumors correlates with clinical benefit. Based on these findings, we hypothesize that the presence of neoepitope-specific CD8+ T cells within the infusion product of ACT is a key determinant of clinical benefit. We apply in silico prediction of neoepitopes along with DNA-barcoded dextran multimer libraries to screen for personal neoepitope-specific CD8+ T cells. We show persistence of neoepitope-specific CD8+ T cells within patient peripheral blood for up to 24 months after therapy. Furthermore, we show an almost complete lack of neoepitope-specific CD8+ T cells within the infusion products of patients with progressive disease. However, patients with stable disease and long-term responses only have a modest increase in the number of targeted neoepitopes, as wells as the total frequency of neoepitope-specific CD8+ T cells. For future experimentation, we therefore aim to include more patients as well as study the phenotypical differences within the pool neoepitope-specific CD8+ T cells, the ultimate goal being a better understanding of what parameters from neoepitope-specific CD8+ T cells correlate with clinical efficacy of ACT.
Citation Format: Nikolaj Pagh Kristensen, Christina Heeke, Siri A. Tvingsholm, Anne-Mette Bjerregaard, Arianna Draghi, Amalie Kai Bentzen, Rikke Andersen, Marco Donia, Inge Marie Svane, Sine Reker Hadrup. Neoepitope-specific CD8+ T cells in adoptive T-cell transfer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A14.
Abstract A26: Towards the identification of novel tumor antigens in human lung cancer
Authors: Chiou Shin-Heng , Tseng Diane , Yang Xinbo , Reuben Alexandre , McSween Alana , Wilhelmy Julie , Wang Chunlin , Shrager Joseph , Zhang Jianjun (Jay) , Garcia K. Christopher , Mackall Crystal , Davis Mark M 
Published: March 2020

Abstract
Immunotherapy has changed the treatment paradigm for patients with lung cancer and other solid tumors, but little is known about the antigen specificities of the T cell residing in tumors. In order to identify novel shared tumor antigens, we have previously developed an algorithm that allows the inference of T-cell specificities based on shared motifs within the T-cell receptor (TCR) CDR3 sequences. Leveraging with a dataset of 789K CDR3 sequences from 178 HLA-typed non-small cell lung cancer (NSCLC) patients, we have found up to 40K motifs after applying stringent cutoffs. Publicly available CDR3 sequences from various tetramer databases assisted with robust assignments of unique T-cell clones from the NSCLC cohorts to known specificities. For example, we have identified and validated multiple tumor-infiltrating T-cell clones that are specific to viral antigens. Furthermore, the availability of HLA genotype results for our lung cancer cohorts facilitated prediction of motifs that are potentially “restricted” to a given HLA allele or supertype. Together with single cell-sorted T-cell clones from our Stanford NSCLC cohort (n = 5,448), we have narrowed down to 60 tumor-specific CDR3 motifs (wherein at least one Stanford sequence could be found) that are potentially restricted to the A02 allele. Within these top A02-enriched motifs, 49 candidates TCR alpha/beta pairs were identified. In an effort to find novel tumor antigens, we prioritized four top T-cell candidates and screened A02 yeast display libraries with distinct peptide length (8-11mer). Four rounds of repeated screens led to the enrichment of a few dominant mimotopes with similar sequences. Database search identified a near-perfect match to a peptide 9mer from the TMEM161A locus that is predicted to bind HLA-A02 with high affinity. Functionally, the synthetic TMEM161A peptide 9mer stimulated Jurkat cells expressing the specific TCR alpha/beta chains as well as the top mimotopes. In conclusion, our results highlight the robustness of our current pipeline for the identification of novel shared tumor antigens. The ongoing work involves further characterizing the functional state of these specific T cells within the tumor microenvironment.
Citation Format: Shin-Heng Chiou, Diane Tseng, Xinbo Yang, Alexandre Reuben, Alana McSween, Julie Wilhelmy, Chunlin Wang, Joseph Shrager, Jianjun (Jay) Zhang, K. Christopher Garcia, Crystal Mackall, Mark M Davis. Towards the identification of novel tumor antigens in human lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A26.
Abstract A27: Training an immuno-army: Exploiting immunoengineering for the treatment of glioblastoma
Authors: Ferber Shiran , Cryer Alexander M. , Gorelick Noah , Tyler Betty , Brem Henry , Langer Robert S. , Artzi Natalie 
Published: March 2020

Abstract
Gliomas are the most common solid tumors and the greatest cause of cancer-related deaths among children in the U.S. Treatment for this group of heterogeneous malignancies involves surgery and chemotherapy; however, tumor recurrence is inevitable. Immunotherapy is a treatment modality that can stimulate the intrinsic immune defenses of the body to eliminate tumor cells. This has been challenging for gliomas, though, due to the exclusionary anatomic barriers and the immunologically quiescent environment of the brain. This project aims to develop an injectable hydrogel patch for controlled local delivery of combination immunotherapy directly to the postsurgical formed cavity of the brain to treat residual disease and to prevent tumor recurrence. Using the hydrogel patch, we seek to overcome the delivery and immunosuppressive barriers of the brain by locally releasing, as a programmed regimen, the following immunomodulatory entities: i) C-X-C motif chemokine 10 (CXCL10; to promote T-lymphocyte recruitment), ii), a new generation of programmed death-ligand 1 (PD-L1) inhibitors (to prevent T-cell exhaustion), iii) FMS-like tyrosine kinase 3 ligand (FLT3L; to induce differentiation and expansion of dendritic cells), and iv) a stimulator of interferon genes (STING) agonist (to trigger cross-priming of CD8+ cytotoxic T cells). Our novel technology possesses the flexibility to personalize an array of antigens/adjuvants or other components of immunotherapy and enables the prevention of brain metastasis by creating an immunologically inhospitable setting for circulating tumor cells. As pediatric gliomas are notoriously resistant to treatment, our hydrogel formulation seeks to address an unmet clinical need for more effective therapeutic modalities.
Note:This abstract was not presented at the conference.
Citation Format: Shiran Ferber, Alexander M. Cryer, Noah Gorelick, Betty Tyler, Henry Brem, Robert S. Langer, Natalie Artzi. Training an immuno-army: Exploiting immunoengineering for the treatment of glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A27.
Abstract A32: Characterizing patterns of cytokine coexpression with immune checkpoint markers in CD4 and CD8 tumor-infiltrating lymphocytes
Authors: Jackson Christopher M. , Dinalankara Wikum , Choi John , Nirschl Thomas R. , Kochel Christina M. , Pant Ayush , Routkevitch Denis , Saleh Laura , Jackson Christina , Skaist Alyza M. , Gupta Anuj , Snyder Linda A. , Schaeffer Edward M. , Ross Ashley E. , Carter Ballentine , Allaf Mohamad E. , Bivalacqua Trinity J. , DeMarzo Angelo M. , Weingart Jon D. , Bettegowda Chetan , Brem Henry , Pardoll Drew M. , Marchionni Luigi , Drake Charles G. , Lim Michael 
Published: March 2020

Abstract
In recent years, immunotherapy has become one of the most exciting and promising avenues to cancer treatment. Treatment with immune checkpoint inhibitors has managed to produce long-term remission of solid tumors in many patients. However, patients who respond well to such treatment are often a minority; this is particularly the case with some cancers such as renal cell carcinoma, non-small cell lung cancer, and glioblastoma, where many patients either derive no benefit or only a short-term benefit. In this analysis, we examined gene expression data from RNA sequencing experiments that compared tumor-infiltrating lymphocytes (TIL) with paired circulating lymphocytes from patients with renal cell carcinoma (RCC), bladder cancer (BLCA), prostate cancer (PRAD), and glioblastoma (GBM). Our analysis helped to characterize global CD4 and CD8 TIL gene expression patterns among these four cohorts. Further, using the expression profiles for known immune checkpoint markers PD-1, TIM-3, and LAG-3 in CD8 cells, we dichotomized the patient samples into potential checkpoint inhibitor responder and nonresponder groups. This model was then used to identify other genes that are associated with CD8 TIL exhaustion, which may lead to the identification of cytokines useful in discovering specific therapeutic targets.
Citation Format: Christopher M. Jackson, Wikum Dinalankara, John Choi, Thomas R. Nirschl, Christina M. Kochel, Ayush Pant, Denis Routkevitch, Laura Saleh, Christina Jackson, Alyza M. Skaist, Anuj Gupta, Linda A. Snyder, Edward M. Schaeffer, Ashley E. Ross, Ballentine Carter, Mohamad E. Allaf, Trinity J. Bivalacqua, Angelo M. DeMarzo, Jon D. Weingart, Chetan Bettegowda, Henry Brem, Drew M. Pardoll, Luigi Marchionni, Charles G. Drake, Michael Lim. Characterizing patterns of cytokine coexpression with immune checkpoint markers in CD4 and CD8 tumor-infiltrating lymphocytes [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A32.
Abstract A37: Blockading PD1 on tumor-primed CD4 T cells instigates antitumor immunity
Authors: Hao Xingxing , Falo Louis D. , Chen Guo , Carey Cara D. , Falo Louis D. , You Zhaoyang 
Published: March 2020

Abstract
Despite the remarkable treatment benefits associated with interventional checkpoint PD1 blockade in cancer, most patients ultimately progress on therapy. Revealing mechanisms underlying tumors responsive to PD1 blockade is critical to identifying biomarkers for predicting responses to PD1 therapy and developing novel PD1 combined therapeutic regimens for their broad use in clinic. In a clinically reflective mouse model of spontaneous metastatic breast carcinoma, effective and durable PD1 therapy is dependent on systemic immunity including Type 1 conventional dendritic cells (cDC1: CD8Î±+DC/CD103+DC), B cells, CD4 T cells, and CD8 T cells. Increased circulating and/or tumor-infiltrating IL12+CD103+DC and IL2+CD4/CD8 T cells are associated with tumors responsive to PD1 therapy. PD1 blockade results in tumor-primed CD44+IL2+CD4 T cells in the periphery regardless of cDC1. Adoptive transfer of PD1 blockade-driven CD44+CD4 T cells ignites protective immunity against new tumors. Neutralization of IL2 post the adoptive transfer abrogates the antitumor immunity. These data suggest the prominent role of PD1 blockade on tumor-primed CD4 T cells in newly induced T cells via cDC1 in response to PD1 therapy.
Citation Format: Xingxing Hao, Louis D. Falo III, Guo Chen, Cara D. Carey, Louis D. Falo Jr., Zhaoyang You. Blockading PD1 on tumor-primed CD4 T cells instigates antitumor immunity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A37.