bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1927: Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning
Authors: Yeh Shan-Ju , Chen Ruoqiao , Xing Jing , Sun Mengying , Liu Ke , Paithankar Shreya , Zhou Jiayu , Chen Bin 
Published: June 2022

Abstract
Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. We present TransCell, a two-step deep transfer learning framework that utilizes the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Compared to the five state-of-art methods, TransCell has the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and has comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, TransCell demonstrates its remarkable predictive power that enables in silico molecular characterization of understudied cell lines.
Citation Format: Shan-Ju Yeh, Ruoqiao Chen, Jing Xing, Mengying Sun, Ke Liu, Shreya Paithankar, Jiayu Zhou, Bin Chen. Transcell: In silico characterization of genomic landscape and cellular responses from gene expressions through a two-step transfer learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1927.
Abstract 1936: MethylationToRegulation: A deep-learning approach to infer chromatin properties from DNA methylomes
Authors: Putnam Daniel K. , Abraham Brian J. , Chen Xiang 
Published: June 2022

Abstract
Gene regulation is critical for cell identity, and its dysregulation is a defining characteristic of common diseases including cancers. Although promoter activity is a strong predictor of gene expression, activities at other regulatory elements, including enhancers and super-enhancers (SE), are major contributors to gene regulation. For example, distinct transcription factor-regulating SEs define neuroblastoma (NB) subtypes with distinct clinical outcomes. However, technical limitations largely prevent ChIP-seq based enhancer/SE activity profiling in primary patient samples. We previously developed MethylationToActivity (M2A) and demonstrated that high-order DNA methylation (DNAm) features are strong predictors of promoter activity measured by ChIP-seq. This tool is important because genomewide DNAm assays are widely used in clinic to classify tumors and stratify patients on clinical trials. However, it is limited by its reliance on known gene position annotations. Here we present MethylationToRegulation (M2R), a method that utilizes a convolutional neural network (CNN)-based deep learning framework to infer intergenic enhancer/SE activities from DNA methylomes. We obtained paired WGBS and H3K27ac ChIP-seq data for 16 pediatric NB samples profiled in the Pediatric Cancer Genome Project. M2R was trained on 6 samples and tested on the remaining 10 samples. It achieved an average relative prediction accuracy of 84% on test samples when compared to the H3K27ac ChIP-seq replicate consistency from the ENCODE project. We adapted the Rank Ordering of Super-Enhancers algorithm to interpret H3K27ac signals inferred from DNA methylomes to identify SEs. M2R faithfully captured subtype-defining SEs with high specificity, including those associated with master NB transcription factors. Our results demonstrate that M2R accurately quantifies enhancer/SE activities and infers critical epigenetic marks from DNA methylomes. Application of M2R will enable the profiling of epigenetic dysregulation in patient tumor samples, seeking to improve clinical outcomes.
Citation Format: Daniel K. Putnam, Brian J. Abraham, Xiang Chen. MethylationToRegulation: A deep-learning approach to infer chromatin properties from DNA methylomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1936.
Abstract 2: Flavokawain A targets cancer stem cells for inhibiting the growth of prostate cancer
Authors: Song Liankun , Mino Merci , Yamak Jana , Nguyen Vyvyan , Lopez Derron , Pham Victor , Fazelpour Ali , Le Vinh , Fu Dongjun , Tippin Matthew , Zi Xiaolin 
Published: June 2022

Abstract
Prostate cancer stem cells (PCSC) are small tumor subpopulations capable of self-renewal and driving prostate cancer heterogeneity, which is critical for cancer initiation, recurrence, and development of therapeutic resistance. Thus, there’s an urgent need to explore and develop new CSC targeting agents. Flavokawain A (FKA), a novel chalcone from kava plant, can selectively inhibit the growth of pRb deficient cell lines and result in a proteasome-dependent and ubiquitination-mediated Skp2 (S-phase kinase-associated protein 2) degradation, while the potential of FKA to target PCSC is unknown. Therefore, we evaluated the effects of FKA on PCSC self-renewal both in vitro and in vivo. FKA treatment decreased both size and numbers of the tumor spheroids growing from CD44+/CD133+ tumor stem cells, which were sorted out from the prostate tumor cell line DU145 and 22RV1. Expression of the stem cell markers Nanog, Oct4, and Sox2 were all downregulated in the cancer spheroids treated with FKA. Growth of the 22RV1CD44+/CD133+ xenograft tumors was significantly inhibited in FKA diet-fed mice compared to the vehicle control diet-fed mice. Immunohistochemistry analysis revealed less positive Ki67, Nanog, and Oct4 cells in tumor tissues from the FKA dietary group than those from the control dietary group. These results demonstrated that FKA can inhibit prostate cancer stemness and suggested a potential role of FKA for preventing prostate cancer recurrence by targeting PCSC.
Citation Format: Liankun Song, Merci Mino, Jana Yamak, Vyvyan Nguyen, Derron Lopez, Victor Pham, Ali Fazelpour, Vinh Le, Dongjun Fu, Matthew Tippin, Xiaolin Zi. Flavokawain A targets cancer stem cells for inhibiting the growth of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2.
Abstract 200: Microtube Array Membrane-Hollow Fiber Assay (MTAM-HFA): A combination of immunocheckpoint blocker (ICBs) and secondary drug anti-cancer drug screening system with significant clinical value propositions for personalized medicine and pre-clinical drug development
Authors: Huang Wan-Ting , Chew Chee Ho , Chen Amanda , Lee Kang-Yuan , Lee Hsing-Lun , Feng Po-Hao , Chiou Jeng-Fong , Lin Kuan-Chou , Wei Po-Li , Chen Chien-Chung 
Published: June 2022

Abstract
Despite modern advances in technology, significant challenges still plague the development of new cancer drugs and cancer care. To address these issue, we are introducing our novel platform technology- Microtube Array Membrane-Hollow Fiber Assay (MTAM-HFA) that is based on combination of the patented MTAM membrane with unique microstructures; replacing the role of traditional hollow fibers enabled the entire HFA assay to be significantly improved in terms of clinical relevance, accuracy, reliability and cost resulting in unprecedented value propositions as an anti-cancer drug screening platform. In the current work, we have clinically demonstrated in several cases where the MTAM-HFA system is capable of accurately predicting clinical response in several Cancers-Lung, Breast and Colon cancers; with unprecedented flexibility of being screened against multiple drug class (including anti-PD1/PDL1) in monotherapy and combination therapy settings. Despite being a phenotypic based assay, the test cycle of MTAM-HFA is only 7-10 days while maintaining a very low cost of up to 60% savings when compared to traditional models such as Patient Derived Xenografts (PDX). When screening ICBs, without the need to use Genetically Engineered Mice (GEM) translates to a cost savings of 98% just for the animal model alone. The combined value proposition of MTAM-HFA makes is a suitable system fulfilling the needs of multiple stakeholders.
Citation Format: Wan-Ting Huang, Chee Ho Chew, Amanda Chen, Kang-Yuan Lee, Hsing-Lun Lee, Po-Hao Feng, Jeng-Fong Chiou, Kuan-Chou Lin, Po-Li Wei, Chien-Chung Chen. Microtube Array Membrane-Hollow Fiber Assay (MTAM-HFA): A combination of immunocheckpoint blocker (ICBs) and secondary drug anti-cancer drug screening system with significant clinical value propositions for personalized medicine and pre-clinical drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 200.
Abstract 2029: Multiomic analysis of whole transcriptome and high plex protein assays on a single FFPE slide
Authors: Bonnett Shilah , Confuorto Nicholas , Fuhrman Kit , Ong Giang , Rosenbloom Alyssa , Lyssand John , Geiss Gary , Beechem Joseph 
Published: June 2022

Abstract
The GeoMx࣪ Digital Spatial Profiler (DSP) enables high-plex, high-throughput spatial profiling and quantification from a single slide for either protein or RNA. To fully understand the interplay between RNA and protein in tissue, we have developed a novel multi analyte assay that allows for the profiling of both analytes from the area of interest (AOI) on a single slide. Here we describe the development and performance of the multi analyte assay on cell pellet array (CPA) and various tissues including tonsil and colorectal cancer (CRC) using a high plex GeoMx Protein Panel and the GeoMx Human Whole Transcriptome Atlas (WTA). We successfully identified conditions to detect RNA and protein simultaneously, with comparable sensitivity and specificity to the single analyte conditions. The data accurately matched cell lines in an unbiased correlation analysis between GeoMx WTA and the entire CCLE RNAseq database. Furthermore, the assay performance was maintained in tissue samples. Tonsil and colorectal cancer biopsies were profiled for RNA (whole transcriptome) and protein from the same AOI, allowing simultaneous measurements of transcriptional and translational regulation of key biological pathways. This multi-analyte profiling enables deeper characterization of precious biological samples that are available in limited quantities.
Citation Format: Shilah Bonnett, Nicholas Confuorto, Kit Fuhrman, Giang Ong, Alyssa Rosenbloom, John Lyssand, Gary Geiss, Joseph Beechem. Multiomic analysis of whole transcriptome and high plex protein assays on a single FFPE slide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2029.
Abstract 2068: An ADCC enhanced anti-CCR8 antibody, which preferentially depletes tumor regulatory T cells and inhibits tumor growth
Authors: Haque Jamil A. , Domeier Cristina , Algate Paul A. , Liu Zhi , Yan Wei , Peng YuFeng 
Published: June 2022

Abstract
Tumor associated FOXP3+ regulatory T cells (Tregs) suppress antitumor immunity, thereby hindering protective immunosurveillance of tumors and hampering effective antitumor immune responses in tumor-bearing hosts. Eliminating the suppressive effects of tumor associated Tregs could, therefore, enhance antitumor activity of existing immunotherapies. CCR8 is a seven transmembrane G-coupled protein whose expression is highly upregulated on tumor associated Tregs in several types of tumors, but not on peripheral Tregs. The specific expression on tumor associated Tregs makes CCR8 an ideal target for treating cancers. The chemokine CCL1 interacts with the N terminus and second extracellular domain of CCR8. CCL1 produced by tumor associated macrophages can induce Tregs migration to the tumors. PSB114, a humanized anti-hCCR8 IgG1 antibody, was developed to block CCL1 mediated Tregs chemotaxis and deplete tumor associated CCR8-expressing Tregs. PSB114 was affinity matured by yeast display and glyco-modified to enhance its ADCC activity. PSB114 has high binding affinity for human CCR8 without significant binding to other membrane proteins, resulting in a favorable PK in hFcRn transgenic mice (T1/2 &gt; 13 days). PSB114 is highly specific for the activated Tregs with low picomolar EC50 of depletion activity. When tested in bioassays, PSB114 enhances T cell activation and TNFα production from activated PBMCs. In a humanized mouse model, PSB114 preferentially depletes tumor infiltrating Tregs and increases NK and CD8 T cell infiltration within the tumor. Moreover, PBS114 significantly inhibited MC38 tumor growth in hCCR8 knock-in mice. These results demonstrate the potential of PSB114 for treating cancers in human.
Citation Format: Jamil A. Haque, Cristina Domeier, Paul A. Algate, Zhi Liu, Wei Yan, YuFeng Peng. An ADCC enhanced anti-CCR8 antibody, which preferentially depletes tumor regulatory T cells and inhibits tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2068.
Abstract 2101: RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T cell-dependent anti-tumor immunity
Authors: Zhang Zhuo , Luo Lin , Xing Chuan , Chen Yu , Xu Peng , Li Mao , Zeng Ling , Li Chao , Ghosh Sadashib , Manna Deborah Della , Townes Tim , Britt William J. , Wajapeyee Narendra , Sleckman Barry P. , Chong Zechen , Leavenworth Jianmei Wu , Yang Eddy 
Published: June 2022

Abstract
Expanding the utility of immune-based cancer treatments is a clinical challenge due to tumor-intrinsic factors that suppress the immune response. Here we report the identification of tumoral Ring Finger Protein 2 (RNF2), the core subunit of the Polycomb Repressor Complex 1 (PRC1), as a negative regulator of antitumor immunity in various human cancers, including breast cancer. In syngeneic murine models of triple negative breast cancer, we found that deleting genes encoding PRC1 subunits Rnf2 or BMI1 proto-oncogene, polycomb ring finger (Bmi1), or the downstream effector of Rnf2, Remodeling and Spacing Factor 1 (Rsf1), was sufficient by itself to induce durable tumor rejection and establish immune memory by enhancing infiltration and activation of NK and CD4+ T-cells, but not CD8+ T-cells, into the tumor and enabled their cooperativity. These findings uncover an epigenetic reprogramming of the tumor-immune microenvironment which fosters durable antitumor immunity and memory.
Citation Format: Zhuo Zhang, Lin Luo, Chuan Xing, Yu Chen, Peng Xu, Mao Li, Ling Zeng, Chao Li, Sadashib Ghosh, Deborah Della Manna, Tim Townes, William J. Britt, Narendra Wajapeyee, Barry P. Sleckman, Zechen Chong, Jianmei Wu Leavenworth, Eddy Yang. RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T cell-dependent anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2101.
Abstract 2104: NK cell immunosurveillance of tumors is regulated by NFAT1 and NFAT2
Authors: Märklin Melanie , Holzmayer Samuel , Kaban Kübra , Müller Martin R. , Salih Helmut R. 
Published: June 2022

Abstract
NK cells are lymphoid components of innate immunity and play an important role in tumor immunosurveillance. One of the major transcriptional regulators in lymphoid cells is NFAT (Nuclear Factor of Activated T cells), controlling lymphocyte development and activity. However, while the role of NFAT signaling is well defined in T cells, the cytotoxic lymphocytes of adaptive immunity, surprisingly little is known regarding the relevance of this transcription factor family in NK cells as effector cells of innate immunity. Available data indicate that NFAT activity is dispensable for development of NK cells. However, several lines of evidence including reports on the effects of the immunosuppressive drugs cyclosporin A and tacrolimus, which mediate their effects through inhibition of calcineurin and consecutively NFAT, implicate an involvement of the NFAT family in NK cell function. We here employed different genetic mouse models to unravel the role of NFAT1 (NFATc2) and NFAT2 (NFATc1) in NK cell reactivity.
When NK cells with knockout (KO) of NFAT1 or NFAT2 compared to NK cells of control mice (WT) were employed in in vitro analyses, lack of either NFAT was found to surprisingly result in enhanced NK cell degranulation as well as increased production of granzyme B and perforin upon stimulation of activating receptors like NK1.1 or Nkp46 or upon co-culture with different leukemia and solid tumor tumor cells. In line, cytotoxicity assays revealed increased lysis of YAC-1 and B16F10 tumor cells by both NFAT1- and NFAT2-deficient NK cells as compared to WT controls. The inhibitory effect of NFAT transcription factors on NK cell effector function could also be confirmed in vivo by employing WT and NFAT KO animals in syngeneic B16F10 melanoma and RMA-S flank tumor models, which revealed a significantly reduced tumor burden in NFAT1 and NFAT2 KO mice. Comparative analyses with single NFAT as well as NFAT1+NFAT2 double KO and WT animals further confirmed the inhibitory effect of NFAT1 and NFAT2 and pointed to additive effects of NFAT1 and NFAT2 in NK cell tumor immunosurveillance.
Taken together, our results provide the first evidence for the direct functional involvement of NFAT1 and NFAT2 in NK cell antitumor reactivity and, in contrast to T and B cells, identify NFAT as a negative regulator of NK cell function.
Citation Format: Melanie Märklin, Samuel Holzmayer, Kübra Kaban, Martin R. Müller, Helmut R. Salih. NK cell immunosurveillance of tumors is regulated by NFAT1 and NFAT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2104.
Abstract 2125: Towards a spatial view of immune cell function in cancer
Authors: Pourmaleki Maryam , Jones Caitlin J. , Greenstein Brian D. , Mellinghoff Sabrina D. , Navarrete Daniel A. , Mehta Smrutiben A. , Socci Nicholas D. , Mellinghoff Ingo K. , Hollmann Travis J. 
Published: June 2022

Abstract
Immunotherapy can result in lasting tumor regressions, but despite its success, only a subset of patients and cancer types benefit from immunotherapy. Thus, uncovering features of the tumor microenvironment (TME) that contribute to this differential response can inform candidates for novel therapies and biomarkers for patient stratification. Recent advances in single-cell technologies allow for profiling of cell states and their spatial interactions within a tumor. Here, we performed multiplexed immunofluorescence (mpIF), a method for in situ single-cell measurement of 30+ proteins, as well as bulk transcriptomics and genomics on 180 tumor samples across 4 immunotherapy-responsive and -resistant solid and liquid cancers: in-transit melanoma (ITM), non-small cell lung cancer (NSCLC), glioblastoma multiforme (GBM), and classical Hodgkin lymphoma (cHL). In aggregate, we measured over 100 million single cells and identified over 1,000 unique tumor and immune cell states. We uncovered immune-suppressive cell states, such as macrophages negative for PD-L1 and B7-H3 in immunotherapy-resistant ITM tumors and all GBM tumors, which generally fail to respond to immunotherapy. In GBM, macrophages exhibited two distinct spatial topologies, infiltrated or excluded. In ITM, we identified pre-treatment cell states and gene expression signatures that associate with immunotherapy response such as MHC class I expression on the tumor cell surface, B cell aggregates, “exhausted” PD-1/LAG-3/TIM-3 triple-positive CD8+ T cells, and expression of interferon-gamma genes. We observed a similar immune checkpoint-rich (PD-1/LAG-3/TIM-3 triple-positive) TME in all cHL tumors, which have remarkably high immunotherapy response rates. We spatially defined the microniche (30-micron radius neighborhood) of “exhausted” CD8+ T cells, and within the microniches, found antigen presentation competent tumor cells, proliferating T cells, and B7-H3 positive macrophages, which together contribute to an activated TME. Together, we present a statistical workflow for the integrated analysis of spatially resolved multidimensional data for cancer target discovery that is tailored towards application in routinely collected formalin-fixed paraffin-embedded cancer biospecimens.
Citation Format: Maryam Pourmaleki, Caitlin J. Jones, Brian D. Greenstein, Sabrina D. Mellinghoff, Daniel A. Navarrete, Smrutiben A. Mehta, Nicholas D. Socci, Ingo K. Mellinghoff, Travis J. Hollmann. Towards a spatial view of immune cell function in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2125.