bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-015: Ex-vivo stimulation of chimeric antigen receptor T cell pre-infusion products predicts clinical response in pediatric B cell acute lymphoblastic leukemia
Authors: Woodhouse Steven , Bai Zhiliang , Fan Rong , Camara Pablo G. , Melenhorst J. Joseph 
Published: December 2020

Abstract
CAR T cell therapy has shown remarkable efficacy against refractory hematological malignancies, frequently leading to complete remission. However, some patients do not respond to the therapy, and many patients who do show an initial response eventually relapse. The factors determining these diverse patient responses remain to be understood. We sought to assess whether the intrinsic molecular characteristics of CAR T pre-infusion products could be predictive of clinical outcomes, reasoning that differences in T cell cellular states and subtype proportions determine response. To investigate the heterogeneity and temporal dynamics of CD19-targeted CAR T cells at a molecular level and the relationship to clinical variables in pediatric B cell acute lymphoblastic leukemia, we profiled by single-cell RNA-seq patient-derived pre-infusion CAR T cells before and after stimulation ex-vivo by antigen presenting cells. Computational analysis of data from 12 pediatric patients with chemotherapy-resistant or refractory disease revealed distinct populations of T cells associated with clinical response. We found that CAR T cells from patients with a favorable response had an increased potential to transition to an active, cytokine-expressing state upon stimulation with CD19, and that responding patients were particularly associated with a robust mixed CD4/CD8 Type 1 helper-like response. Conversely, we found that patients who do not did not respond to CAR T therapy had a higher proportion of non-cytokine expressing CD8 cytotoxic T cells upon stimulation. These results demonstrate the potential of single-cell gene expression profiling coupled with computational analysis to uncover the molecular factors determining response to immunotherapy.
Citation Format: Steven Woodhouse, Zhiliang Bai, Rong Fan, Pablo G. Camara, J. Joseph Melenhorst. Ex-vivo stimulation of chimeric antigen receptor T cell pre-infusion products predicts clinical response in pediatric B cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-015.
Abstract PO-026: GLUER: integrative analysis of multi-omics data at single-cell resolution
Authors: Peng Tao , Pourfarhangi Kamyar Esmaeili , Tan Kai 
Published: December 2020

Abstract
Single-cell omics assays such as RNA-Seq, ATAC-Seq and methylome sequencing have been developed to identify cell types and/or states in heterogeneous tissues. However, it is challenging to integrate these different types of single-cell omics data. Moreover, the advent of spatially resolved single-cell imaging data represent another challenge for integrative analysis with omics data. Here, we present a new algorithm, inteGrative anaLysis of mUlti-omics at single-cEll Resolution (GLUER), for integration of single-cell multi-omics data as well as imaging data. We tested GLUER using multiple datasets generated using multiomics data generated on the same single cells, which was taken as the ground truth. Our results demonstrate that GLUER has significantly improved performance in terms of the accuracy of matching cells with different data modalities, which in turn enhances downstream analyses such as clustering and trajectory inference. GLUER provides a principled analytical framework for studying the heterogeneity of cell populations using multi-omics and imaging data.
Citation Format: Tao Peng, Kamyar Esmaeili Pourfarhangi, Kai Tan. GLUER: integrative analysis of multi-omics data at single-cell resolution [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-026.
Abstract PO-050: Peripheral neurons invade oral squamous cell carcinoma microenvironment and drive tumorigenesis
Authors: Atherton Megan A. , Nilsen Marci L. , Scheff Nicole N. 
Published: December 2020

Abstract
The impact of peripheral neurons on carcinogenesis is an understudied process in head and neck cancer. Peripheral nerve innervation is increased in preclinical models of oral cancer; sympathectomy resulted in smaller, less invasive cancers. Local neurotransmitter release from peripheral neurons innervating cancer has been linked to cancer growth and immune suppression. We hypothesize that local neurotransmitter release from trigeminal sensory neurons (TGNs) and sympathetic postganglionic neurons promotes cancer proliferation and suppresses the immune response. We used real-time PCR to determine RNA expression in human oral cancer cell lines and a colorimetric cell proliferation assay to quantify cancer cell growth in response to the sympathetic and sensory neurotransmitters. Oral cancer cell lines, HSC-3 and SCC-4, overexpress the norepinephrine (NE) receptor, adrenergic receptor beta 2 (ADRβ2) and sensory neurotransmitter receptors, receptor activity modifying protein1 (RAMP1) and neurokinin1 receptor (NK1R) compared to the non-tumorigenic cell line, HaCaT. Treatment with sympathetic (NE) and sensory (CGRP, substance p) neurotransmitters for 48 hours significantly increased cell proliferation in HSC-3 (&gt;2-fold) and SCC-4 (&gt;1.5-fold) cell lines, but had no effect on HaCaT cell proliferation. Using optical clearing and immunohistochemistry, we observed increased PGP9.5+ neuronal fiber density in the microenvironment using high-resolution microscopy in a tongue oral cancer xenograft mouse model. In vitro we measured a 44.6 ± 1.14% increase in TGN sprouting after 48-hour exposure to conditioned media from the HSC-3, compared to conditioned media from HaCaT. Lastly, HSC-3 cell culture supernatant injection (50 µl) into the tongue of C57Bl/6 female mice resulted in infiltration of CD45+ immune cells (9.10 ± 1.2 % of total live cells). Temporary nerve block with 1% bupivacaine injection into the lingual nerve prior to a 50 µl injection of HSC-3 supernatant into the tongue resulted in significantly more CD45+ immune cell infiltration (21.66 ± 3.4 %) compared to HSC-3 supernatant without pharmacologic nerve block. These results together suggest neurotransmitter-induced increase in oral cancer cell proliferation and neurotransmitter-induced suppression of the cancer-evoked immune response. Understanding the nerve-cancer interaction might improve strategies to treat head ad neck cancer by targeting peripheral neurons in the cancer microenvironment.
Citation Format: Megan A. Atherton, Marci L. Nilsen, Nicole N. Scheff. Peripheral neurons invade oral squamous cell carcinoma microenvironment and drive tumorigenesis [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-050.
Abstract PO-099: SOX2 delineates a mouse lung adenocarcinoma subtype vulnerable to targeted therapy
Authors: Cooper Jonathan E. , Daemen Anneleen , Nickles Dorothee , Myrta Szymon , Foreman Oded , Eastham Jeff , Junttila Melissa R. , Jasper Heinrich 
Published: December 2020

Abstract
Lung adenocarcinomas comprise the largest fraction of non-small cell lung cancer, which is the leading cause of cancer deaths. 75% of adenocarcinomas lack targeted therapies due to scarcity of druggable drivers. We leveraged transcriptional data from &gt;800 early-stage and advanced patients to classify tumors based on signaling similarities and discover subgroups within this unmet patient population. The subtypes capture heterogeneity even amongst tumors lacking known oncogenic drivers. Paired multi-regional intratumoral biopsies demonstrate unified subtypes despite divergently evolved pro-oncogenic mutations, indicating subtype stability during selective pressure. We identified differential subtype response to MEK inhibition across multiple preclinical model systems and a clinical trial, supporting prognostic utility of transcriptional subtyping. Differential subtype dependency on MEK signaling reproduced in a mouse model of KRAS-mutant lung adenocarcinoma, where a MEK-dependent adenocarcinoma subtype is driven by a SOX2 cellular state. Our findings support forward translational relevance of transcriptional subtypes and reveal that naturally evolved yet ectopic expression of a pioneer transcription factor may modulate tumor subtype and response.
Citation Format: Jonathan E. Cooper, Anneleen Daemen, Dorothee Nickles, Szymon Myrta, Oded Foreman, Jeff Eastham, Melissa R. Junttila, Heinrich Jasper. SOX2 delineates a mouse lung adenocarcinoma subtype vulnerable to targeted therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-099.
Abstract PO-125: Targeting histone methylation to overrule transcriptionally driven drug resistance in myeloid leukemia
Authors: van Gils Noortje , Verhagen Han J.M.P. , Martiáñez Tània , Denkers Fedor , Vermue Eline , Rutten Arjo , Csikós Tamás , Çil Meyrem , Al Marjon , van Gemert Frank , Janssen Jeroen J.W.M. , Ossenkoppele Gert J. , Menezes Renee X. , Smit Linda 
Published: December 2020

Abstract
Standard induction chemotherapy, consisting of an anthracycline and cytarabine, has been the first-line therapeutic to treat acute myeloid leukemia (AML). Although this treatment induces complete remissions (CR) in the majority of patients, many face a relapse. Relapse is caused by the survival of chemotherapy-resistant leukemia cells (minimal residual disease, MRD), that may have acquired drug resistance by non-genetic mechanisms. Persistence of MRD is driven by intra-leukemic heterogeneity and plasticity in response to therapy. Leukemia cells within MRD capable of initiating relapse are thought to have stem cell features and are therefore named “leukemic stem cells” (LSCs). In this study, we demonstrated that the anthracycline doxorubicin epigenetically reprograms leukemia cells by inducing tri-methylation of histone 3 lysine 27 (H3K27) and H3K4. Moreover, to understand chemotherapy resistance at the single-cell level and to study intra-leukemia heterogeneity with respect to anthracycline sensitivity, we seeded K562 myeloid leukemia cells in 480 wells, each containing 10.000 cells, and treated the cells with increasing concentrations of doxorubicin. Using this approach, a subpopulation of reversible anthracycline-tolerant cells (ATCs) was identified within the doxorubicin-sensitive leukemia cell population, which lacked upregulation of H3K27me3 or H3K4me3 and exhibited epigenetically regulated expression of stem cell features similar to leukemic stem cells (LSCs). These ATCs have a distinct transcriptional landscape from the leukemia bulk and could be eradicated by the KDM6 inhibitor GSK-J4. In primary human AML, GSK-J4 treatment could eliminate AML blasts and LSCs at diagnosis but importantly it could significantly reduce chemotherapy resistant AML patient cell load (MRD) and survival of LSCs residing within MRD, ex vivo and in vivo. An efficient response to GSK-J4 was associated with upregulation of H3K27 and/or H3K4 methylation, and downregulation of STAT5B. Together, our results reveal plasticity of anthracycline resistance in AML cells and highlight the potential of epigenetic-based therapeutics to target chemotherapy-resistant AML cells.
Citation Format: Noortje van Gils, Han J.M.P. Verhagen, Tània Martiáñez, Fedor Denkers, Eline Vermue, Arjo Rutten, Tamás Csikós, Meyrem Çil, Marjon Al, Frank van Gemert, Jeroen J.W.M. Janssen, Gert J. Ossenkoppele, Renee X. Menezes, Linda Smit. Targeting histone methylation to overrule transcriptionally driven drug resistance in myeloid leukemia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-125.
Abstract IA01: Clinical Trial Diversity: A Perspective from the FDA Office of Minority Health and Health Equity
Authors: Araojo Richardae 
Published: December 2020

Abstract
The U.S. Food and Drug Administration’s Office of Minority Health and Health Equity (OMHHE) aims to protect and promote the health of diverse populations though research, outreach, and communication that addresses health disparities. A key priority area for FDA OMHHE is advancing racial and ethnic minority participation in clinical trials. This presentation will provide an overview of FDA OMHHE’s efforts to advance diverse participation in clinical trials and highlight FDA policy strategies that support clinical trial diversity.
Citation Format: Richardae Araojo. Clinical Trial Diversity: A Perspective from the FDA Office of Minority Health and Health Equity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA01.
Abstract IA13: Advancing gastric cancer precision medicine through minority patient derived modeling
Authors: Zhang Hongyong , Coggins Nicole , Lott Paul , Estrada Ana , Polanco Guadalupe , Morales Alexa , Rocha Sienna , Kirane Amanda , Urayama Shiro , Torres Javier , Bohorquez Mabel , Echeverry Magdalena , Consortium UCaMP , Carvajal-Carmona Luis G. 
Published: December 2020

Abstract
Gastric cancer is a leading cause of cancer mortality in Latinos, who are two times more likely to die of gastric cancer when compared to non-Latino Whites. Gastric cancer outcomes in this minority are poor as most tumors are detected in the metastatic setting, where five-year survival is less than 5%. Despite such a high mortality burden in Latinos and other minority populations, there are only three molecularly-guided therapies approved by the Food and Drug Administration to treat gastric cancer. To advance precision medicine in minority groups, the NCI Center to Reduce Cancer Health Disparities funded our University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP), which is currently creating and characterizing PDXs and patient-derived organoids from minority patients including those with gastric cancer. In this presentation, we will present an overview of recent advances in gastric cancer precision modeling using patient-derived organoids and xenografts from Latino patients. We will summarize the most promising druggable genes and pathways in gastric tumors and will present initial findings on the development of promising combinations using PIK3CA inhibitors.
Citation Format: Hongyong Zhang, Nicole Coggins, Paul Lott, Ana Estrada, Guadalupe Polanco, Alexa Morales, Sienna Rocha, Amanda Kirane, Shiro Urayama, Javier Torres, Mabel Bohorquez, Magdalena Echeverry, UCaMP Consortium, Luis G. Carvajal-Carmona. Advancing gastric cancer precision medicine through minority patient derived modeling [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA13.
Abstract IA16: Lung Cancer Risk Assessment in Diverse Populations: One Size Cannot Fit All
Authors: Nana-Sinkam Patrick 
Published: December 2020

Abstract
Lung cancer is the leading cause of cancer related deaths in the United States with an estimate of over 200,000 new cases and 135,720 deaths in 2020. Despite the development of precision therapies, immunotherapy and improved surgical techniques, the overall 5-year survival has remained below that of many other malignancies and significant disparities continue to persist. Black American males tend to present with later-stage disease, are less likely to undergo appropriate staging and thus, have a higher lung cancer mortality. The National Lung Screening Trial I (NLST) determined that low-dose CT (LDCT) screening could reduce lung cancer specific mortality by nearly 20% and overall mortality by 6.7%. However, studies suggest that clinically useful models for improved lung cancer risk stratification will be essential to the identification of those most likely to benefit from screening while minimizing unnecessary screening and associated risks. In NLST, only 4% of enrolled participants were Black Americans. Recent investigation demonstrates that current screening eligibility criteria are insufficient in identifying Black Americans at risk for lung cancer a large percentage of whom are diagnosed at a younger age than White Americans and with less tobacco consumption. As a result, current draft recommendations include reducing both age and smoking screening eligibility to 50 years of age and 20 pack years respectively with a goal of narrowing gaps in disparities in early lung cancer diagnosis and outcome. Here, we will review current models for lung cancer risk stratification that incorporate sociodemographic factors, comorbid illnesses and non-invasive biomarkers and discuss their clinical application to diverse populations.
Citation Format: Patrick Nana-Sinkam. Lung Cancer Risk Assessment in Diverse Populations: One Size Cannot Fit All [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA16.
Abstract IA26: Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience
Authors: Sparano Joseph A. 
Published: December 2020

Abstract
Although breast cancer incidence and mortality have declined by about 35% in the United States since 1990, mortality rates have declined less in Black women, contributing to a widening of the racial gap which has contributed to about a 35% higher mortality rate for Black women compared with others. Black women are more likely to present with advanced stage disease, have triple negative breast cancer (TNBC), exhibit greater non-adherence and poorer tolerance to chemotherapy and endocrine therapy, and have more comorbidities and experience more disparities in care. With regard to ethnicity, Hispanic women also exhibit higher rates of TNBC, but otherwise experience similar outcomes as non-Hispanic women. In order to disentangle factors that may be contributing to inferior outcome associated with Black race, we evaluated the association between Black race or Hispanic ethnicity and recurrence in the population served by Montefiore Medical Center and in 3 clinical trials (E1199, E5103, TAILORx) coordinated by the ECOG-ACRIN Cancer Research Group, as summarized in Table 1. The results were remarkably consistent – Black race was associated with significantly higher recurrence risk (1.39-1.84-fold) in multivariate models in ER+ breast cancer, but not ER-negative breast cancer. Similar findings were not observed for Hispanic women. In the TAILORx trial, there were no significant differences in distribution of 21-gene recurrence score, nor ER, PR, or HER2 RNA expression levels, by race or ethnicity. In other analysis, we have reported specific genetic variants associated with higher risk of taxane-induced neuropathy in Black women (PMID: 26138065). Our findings highlight the need for greater representation of racial and ethnic minorities in clinical trials, and that additional studies designed specifically to determine if socioeconomic factors, biological factors, and/or other factors contribute to these disparities. ECOG-ACRIN is currently conducting a clinical trial to prospectively validate genetic variants associated with higher risk of peripheral neuropathy in Black women with breast cancer receiving taxane therapy (EAZ171; NCT04001829).
Citation Format: Joseph A. Sparano. Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA26.
Abstract IA38: A perspective on global cancer disparities from the NCI Center for Global Health
Authors: Gopal Satish 
Published: December 2020

Abstract
Dr. Gopal, Director of the NCI Center for Global Health, will provide an overview of the center, including its work to address global cancer health disparities. Opportunities to synergize health disparities research efforts across domestic and international settings will be discussed.
Citation Format: Satish Gopal. A perspective on global cancer disparities from the NCI Center for Global Health [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA38.
Abstract IA44: Equity and access: Looking upstream to make lasting improvements in cancer outcomes
Authors: Pruitt Sandi L. 
Published: December 2020

Abstract
Many cancer researchers are trained to quantify disparities between racial groups and to identify race as the risk factor. However, if we look upstream, we can identify that structural racism, not race, is a fundamental cause of racial inequity. Likewise, we frequently conceptualize access with a downstream lens, focusing on access to clinical trials or treatment, and we ignore upstream factors such as equitable access to economic opportunity and racial justice. Cancer disparities start where we live, learn, work, and play. These upstream factors, often referred to as the social determinants of health, are increasingly acknowledged, but not well integrated into cancer research and intervention efforts. Examples from recent research will be presented that highlight the role of upstream factors, especially neighborhood factors, in creating and sustaining cancer inequities. Suggestions will be provided for how cancer research can expand beyond our downstream biomedical frameworks in order to correctly identify and intervene on upstream factors that cause inequities in cancer outcomes.
Citation Format: Sandi L. Pruitt. Equity and access: Looking upstream to make lasting improvements in cancer outcomes [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA44.