bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3119: A novel tissue resident memory T cell (TRM) signature predicts prognosis and tumor microenvironment of patients with melanoma
Authors: Jiang Chongming , Li Jianrong , Helman Elena , Shen Xiling , Cheng Chao 
Published: April 2023

Abstract
Background: Melanoma is a prime example of how basic and translational research can improve cancer prognosis The tumor immune microenvironment (TIME) of melanoma is a dynamic, heterogeneous mixture of multiple immune cells and malignant and nonmalignant cells. Tissue resident memory T cells (TRM) may be prognostic for improved melanoma survival and proliferate during treatment with immune checkpoint inhibitors. The role of TRM in melanoma and rare melanoma subtypes is unknown.
Method: Our goal was to examine the relationship between TRM abundance and melanoma prognosis. We generated TRM signatures using multiple independent single-cell RNA sequencing data from human melanoma cells to infer TRM abundance. Lastly, we built a LASSO Cox regression model that predicts patient survival. The TCGA dataset was used as a test group. Model accuracy was validated using Kaplan-Meier survival analysis, receiver operating characteristic curves, principal component analysis, and t-distributed stochastic neighbor embedding.
Findings: We found a significantly longer overall survival in patients with high TRM infiltration. Furthermore, we found that TRM can interact with the tumor microenvironment and genomic features of melanoma, making TRM abundance positively correlate with the prognosis of melanoma patients. Melanoma abundance was also significantly associated with several common genomic aberrations, including the TP53 mutation. In addition, we developed a 20-gene risk score that significantly classifies patients into low- and high-risk categories. We found that in several independent datasets, patients with high risk scores had significantly worse overall survival than patients with low risk scores.
Conclusions: Altogether, our findings suggest that TRM abundance may positively correlate with melanoma survival. We developed a high-precision LASSO Cox regression model based on the new TRM abundance characteristics. Our study shows that this model effectively predicts the prognosis of melanoma patients and may provide new therapeutic targets and measure the effectiveness of melanoma-directed therapies.
Keywords: Tissue resident memory T cell, tumor immune microenvironment, melanoma, prognosis
Citation Format: Chongming Jiang, Jianrong Li, Elena Helman, Xiling Shen, Chao Cheng. A novel tissue resident memory T cell (TRM) signature predicts prognosis and tumor microenvironment of patients with melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3119.
Abstract 3131: Anaplastic transformation model in thyroid cancer revealed by single cell lineage and fate analysis
Authors: Lu Lina , Wang Jennifer Rui , Henderson Ying C. , Bai Shanshan , Yang Jie , Hu Min , Yan Yuanqing , Tran Tuan M , Li Jianzhuo , Shiau Cheng-Kai , Kieser Rachel , Zhao Xiao , Wang Jiping , Nurieva Roza , Williams Michelle D. , Cabanillas Maria E. , Dadu Ramona , Busaidy Naifa Lamki , Zafereo Mark , Navin Nicholas , Lai Stephen Y. , Gao Ruli 
Published: April 2023

Abstract
The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC), however the complex intra-tumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single cell transcriptomes and genetic alterations data of patients with different subtypes of thyroid cancer. The resulting model started from stress-responsive DTC cells to inflammatory ATC cells, to mitotic defective ATC cells and extended all the way to mesenchymal ATC cells. In parallel with tumor cell evolution, macrophages shifted from anti-tumor to tumor-promoting states and T cells reprogrammed from cytotoxic to exhausted states. Further, our analysis identified two important milestones: 1) diploid stage, where ATC cells were commonly diploids with non-RAS mutations and inflammatory phenotypes. 2) aneuploid stage, where ATC cells gained aneuploidy with frequent RAS mutations and mesenchymal phenotypes leading to the extreme lethal stage of ATC progression.
Citation Format: Lina Lu, Jennifer Rui Wang, Ying C. Henderson, Shanshan Bai, Jie Yang, Min Hu, Yuanqing Yan, Tuan M Tran, Jianzhuo Li, Cheng-Kai Shiau, Rachel Kieser, Xiao Zhao, Jiping Wang, Roza Nurieva, Michelle D. Williams, Maria E. Cabanillas, Ramona Dadu, Naifa Lamki Busaidy, Mark Zafereo, Nicholas Navin, Stephen Y. Lai, Ruli Gao. Anaplastic transformation model in thyroid cancer revealed by single cell lineage and fate analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3131.
Abstract 3141: Epiregulon infers single-cell transcription factor activity to dissect mechanisms of lineage plasticity and drug response
Authors: Wlodarczyk Tomasz , Tan Jenille , Seidel Kerstin , Wu Diana , Chen Shang-Yang , Chlebowski Aleksander , Keyes Timothy , Guo Yu , Lun Aaron , Siebel Christopher , Xie Shiqi , Yao Xiaosai 
Published: April 2023

Abstract
Single-cell multiomic technologies enable holistic reconstruction of cell states and hold the potential to identify drivers of tumor evolution and drug resistance. However, the data sparsity of single-cell assays can preclude accurate estimation of transcription factor activity. In addition, gene expression alone cannot capture transcription factor activity, especially in the context of drug treatment which alters transcription factor function without suppressing gene expression. To circumvent these challenges, we have developed epiregulon, a R package that constructs gene regulatory networks and infers transcription factor (TF) activity in single cells by integrating single cell gene expression, chromatin accessibility and bulk TF occupancy data. Epiregulon applies tests of independence to identify likely transcription factor - regulatory element - target gene relationships occurring at joint probabilities exceeding the expected probabilities of independent events. With epiregulon, we are able to detect lineage factor activity at enhanced sensitivity and predict perturbations more accurately than gene expression could. We further applied this tool to understand transcription factor activity to enzalutamide treatment and identify potential drivers of enzalutamide resistance. Finally, we generated a ground truth dataset using reprogram-seq, a technology that captures multi-omic profiles of single cells upon expression of defined transcription factors. Epiregulon correctly predicts NKX2-1 targets and demonstrates that NKX2-1 expression reprograms the epigenome towards a neuroendocrine state in LNCaP cells. Epiregulon is a useful tool that constructs gene regulatory networks to model the underlying gene regulation hierarchies that drive gene expression and cell states.
Citation Format: Tomasz Wlodarczyk, Jenille Tan, Kerstin Seidel, Diana Wu, Shang-Yang Chen, Aleksander Chlebowski, Timothy Keyes, Yu Guo, Aaron Lun, Christopher Siebel, Shiqi Xie, Xiaosai Yao. Epiregulon infers single-cell transcription factor activity to dissect mechanisms of lineage plasticity and drug response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3141.
Abstract 3175: Comprehensive multi-omic characterization of hepatocellular carcinoma in Hispanic patients
Authors: Das Debodipta , Wang Xiaojing , Chiu Yu-Chiao , Bouamar Hakim , Chen Yidong , Zheng Siyuan , Cigarroa Francisco G. , Sun Lu-Zhe 
Published: April 2023

Abstract
Hispanics in the US experience a disproportionate burden of hepatocellular carcinoma (HCC) with an overall incidence and cancer-related mortality nearly two times higher than non-Hispanic whites. The genomic characteristics and underlying molecular mechanisms driving tumorigenesis associated with HCC in Hispanic patients remain unknown. Here, we used 31 paired tumor and adjacent non-tumor liver samples from Hispanic patients in South Texas to perform integrated genomic, transcriptomic, proteomic, and metabolomic analyses. Similar to HCC in other ethnic groups, CTNNB1 and TP53 were found to have the most frequent somatic mutations in the Hispanic HCC. On the other hand, AXIN2 and to a lesser degree MTOR appear more frequently mutated in the Hispanics compared to the various ethnic groups included in The Cancer Genome Atlas (TCGA) study. Somatic mutations in the Hispanic HCC showed signatures of tobacco chewing and aflatoxin exposure, which are different from the signatures found frequently in the liver cancer patients in the TCGA study. The WNT, TP53, & cell cycle were the most frequently altered oncogenic pathways in our cohort. Unsupervised clustering of patients, based on the enrichment scores from single sample Gene Set Enrichment Analysis (ssGSEA) using our tumor and nontumor paired RNA-Seq and proteomic data, revealed two clusters with striking differences in various signaling pathways and cellular functions. A similar clustering pattern with a significant difference in overall survival was seen in the patients from the TCGA study. Irrespective of ethnicity, immune infiltration in the tumor microenvironment and liver function-related pathways were significantly different between patients in these clusters. Integrated transcriptomic, proteomic, and metabolomic analyses identified significant negative enrichments in gluconeogenesis, TCA cycle, and glutamate metabolism in Hispanic HCC. These results suggest the existence of molecular mechanisms either unique in Hispanics or similar to non-Hispanic HCC, especially from the TCGA study. Our findings might provide insights to developing predictive biomarkers for the early diagnosis and novel therapeutics for the management of HCC.
Citation Format: Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun. Comprehensive multi-omic characterization of hepatocellular carcinoma in Hispanic patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3175.
Abstract 3176: Modeling the complex multi-cellular ecosystem of the tumor microenvironment in colorectal cancer using multi-omics data
Authors: Ildefonso Geena , Finley Stacey 
Published: April 2023

Abstract
The high inter-tumoral phenotypic heterogeneity of colorectal cancer exists within the tumor microenvironment (TME), which ultimately contributes to overall tumor survival. Tumor cells, as the center of the tumor microenvironment, employ sophisticated signaling networks to alter the cell fate decisions between cancerous and non-cancerous cells. A complex network of interactions is the source of this intercellular communication, resulting in tumor growth and progression, drug resistance, and ineffective treatment response. Recent experimental developments in colorectal cancer (CRC) have shown that understanding various underlying mechanisms of tumor growth and progression requires an in-depth understanding of the complex interactions between tumor cells and their surrounding microenvironment. Here, we analyze single-cell RNA sequencing data in CRC and construct gene regulatory networks to define interactions and identify cell states within the TME. The gene regulatory networks are incorporated as a multi-cellular ecosystem representing an experiment-based computational model of phenotypic crosstalk within the TME of CRC. The model simulates and predicts the multi-cellular responses to colorectal cancer to probe and identify mechanisms of cell state evolution and decisions resulting from chemo-agents, used to target TME components. This research will further our understanding of the multi-cellular crosstalk underlying the mechanisms within the TME and facilitate the development and optimization of cancer therapies that inhibit tumor growth in CRC.
Citation Format: Geena Ildefonso, Stacey Finley. Modeling the complex multi-cellular ecosystem of the tumor microenvironment in colorectal cancer using multi-omics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3176.
Abstract 3189: Pre-clinical evaluation of novel folate receptor 1 directed CAR T cells for high grade serous ovarian cancer
Authors: Herbel Christoph , Daigre Julie , Martinez-Osuna Manuel , Bethke Maria , Steiner Larissa , Brauner Janina , Kopatz Jens , Praveen Paurush , Eckardt Dominik , Bosio Andreas 
Published: April 2023

Abstract
Purpose: Treatment of ovarian cancer remains challenging. A high unmet clinical need for targeted, efficient, and persisting drugs still is a major issue for clinicians and patients diagnosed with ovarian cancer, particularly platinum-resistant and-refractory, recurrent disease. Genetically modified T cells expressing chimeric antigen receptors (CARs) have shown efficient, as well as persisting anti-tumor functionality in hematological malignancies. However, solid cancers have not yet been as efficiently treated with CAR T cells, potentially due to the lack of appropriate targets. Therefore, we thoroughly characterized FOLR1 as CAR T cell target for ovarian cancer, designed novel CAR T cells, and assessed these drug candidates preclinically in vitro and in vivo.
Experimental Design: We performed ultra-high content imaging on high-grade serous epithelial ovarian cancer as well as healthy tissue samples to profile the expression of the tumor-associated antigen FOLR1. Subsequently, we designed a series of CAR T cell candidates based on different monoclonal antibodies targeting FOLR1, in order to leverage on clinical experience with these binders, particularly safety aspects. The CAR designs differed in the VL-VH orientation and the spacer domain of the CAR construct. The preclinical assessment of various FOLR1-directed CAR T cell constructs was evaluated against various ovarian cancer cell lines in vitro and in vivo.
Results: In this study we show high and consistent expression of the tumor-associated antigen FOLR1 on primary ovarian cancer samples, namely high-grade serous ovarian cancer. Moreover, FOLR1 expression is low, restricted, and polarized in healthy tissues. We generated diverse FOLR1-specific CAR T cells and characterized their efficacy and specificity in vitro as well as in an ovarian cancer xenograft model. CAR T cells rapidly and efficiently eradicate xenograft tumors. This anti-tumor response is accompanied by CAR T cell expansion, FOLR1-dependent cytokine secretion, and infiltration of CAR T cells into the tumor.
Conclusions: These findings demonstrate the feasibility of a preclinical CAR T cell approach targeting FOLR1 as treatment option for ovarian cancer and potentially other FOLR1-expressing tumors.
Citation Format: Christoph Herbel, Julie Daigre, Manuel Martinez-Osuna, Maria Bethke, Larissa Steiner, Janina Brauner, Jens Kopatz, Paurush Praveen, Dominik Eckardt, Andreas Bosio. Pre-clinical evaluation of novel folate receptor 1 directed CAR T cells for high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3189.
Abstract 3236: Optimizing mRNA vaccines and virus-mediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification
Authors: Yang Ming , Richardson Crystal , Rao Prassanna , Koole Cassandra , Karney Michael J. , Kumar Sumit 
Published: April 2023

Abstract
With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest.
Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A high-throughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail.
The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.
Citation Format: Ming Yang, Crystal Richardson, Prassanna Rao, Cassandra Koole, Michael J. Karney, Sumit Kumar. Optimizing mRNA vaccines and virus-mediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3236.
Abstract 3255: Investigate immune regulation and therapeutic efficacy via regorafenib combined with PD-L1 inhibitor in glioblastoma
Authors: Dong Dai-Cheng , Liu Yu-Chiang 
Published: April 2023

Abstract
Glioblastoma (GBM) is one of the most common aggressive primary brain tumors, with poor survival despite after surgery, radiation treatment, and chemotherapy. Regorafenib, a tyrosine kinase inhibitor used for cancer treatment, was known to effectively inhibit angiogenesis and attenuate the activity of oncogene receptor hormones. Currently, regorafenib has been approved to treat various cancer with significant improvement. Though regorafenib show potential to penetrate blood brain barrier, the role of regorafenib in glioblastoma has not been elucidated. With the finding of central nervous lymphatic system, immune checkpoint inhibitor (programmed cell death protein-1 and its ligand) therapy has ongoing with clinical trial in GBM. The PD-L1 on tumor cells may interact with the PD-1 on T cells, and therefore inhibited the proliferation of T cells proliferate and finally cause the immune escape of tumor. While the therapeutic efficacy of using immune checkpoint inhibitor alone is still not significant enough for GBM; thus, it is necessary to find other suitable drugs for combination. Moreover, patient with low PD-L1 expression may not be able to administrate with anti-PD-L1 therapy. Therefore, identifying suitable combination reagent to regulate PD-L1 expression and to enhance efficacy of anti-PD-L1 therapy is important. Our experiment aims to explore whether regorafenib can increase the transcription of PD-L1 via regulating β-catenin-related signal transduction, and thus enhancing the treatment efficacy of immune checkpoint inhibitor (anti-PD-L1) on GBM. Here, we used GL-261 animal model to prove the regulation of regorafenib combined with anti-PD-L1. According to our data, regorafenib can inhibit the proliferation and induce the apoptosis pattern in GBM cells. Further, regorafenib may induce PD-L1 expression via activating β-catenin-related signaling; and therefore, increasing the targeting efficacy of anti-PD-L1 in GBM. Not only induce PD-L1 expression, regorafenib combined with anti-PD-L1 may also induce the accumulation of active cytotoxicity T lymphocytes (CD8+IFN-γ+) and reduce the accumulation of immunosuppressive cells, such as regulatory T cells (CD11b+Gr-1+) and myeloid-derived suppressor cells (CD4+CD25+FOXP3+). In conclusion, our animal experiments suggested that regorafenib may effectively promote PD-L1 transcription in glioblastoma by up-regulating β-catenin-related signaling, thereby increasing the therapeutic target efficacy and effectiveness of immune checkpoint inhibitors.
Citation Format: Dai-Cheng Dong, Yu-Chiang Liu. Investigate immune regulation and therapeutic efficacy via regorafenib combined with PD-L1 inhibitor in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3255.
Abstract 3378: Rapid and efficient sample preparations for cell free DNA
Authors: Zeng Zhiyang , Taft Andrew , Riemersma Kasen , Fitzgerald Connor , Scurria Mike , Hermanson Spenccer , Zhou Wenhui 
Published: April 2023

Abstract
The analysis of cell-free DNA (cfDNA) as a sensitive biomarker for cancer prognosis, diagnosis and monitoring resulted in a need for efficient and fast cfDNA isolation. The traditional cfDNA purification methods using chaotropic solvent to separate nucleic acids from plasma through column or magnetic bead purification processes are usually laborious and time consuming, involving multiple washing steps, and the residual organic solvent could be carried over to the elution solution that could cause downstream PCR inhibition. Herein, we developed a novel particle surface chemistry that can biochemically bind rapidly (&lt;1min) and release nucleic acids rapidly (&lt;1min) under different buffer conditions without needing chaotropic solvent. We further optimized the binding and elution buffer solutions that allow to isolate cfDNA from plasma within 5-10 minutes in the sample volumes from 1 ml to 4 ml. The real-time quantitative PCR indicated DNA extraction yields were comparable or slightly better than the traditional methods for both small and large volumes. The novel bead chemistry and the optimized binding and elution buffers are not only compatible to high throughput format but could also be applied to a variety sample types for rapid sample preparations.
Citation Format: Zhiyang Zeng, Andrew Taft, Kasen Riemersma, Connor Fitzgerald, Mike Scurria, Spenccer Hermanson, Wenhui Zhou. Rapid and efficient sample preparations for cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3378.