bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A010: Evaluation of the Avantect Pancreatic Cancer Test for identifying high-risk pancreatic cysts
Authors: Bergamaschi Anna , Haan David , Friedl Verena , Guler Gulfem , Kesling Michael , Collins Micah , Hazen Kyle , Lopez Vanessa , Malta Roger , Nabiyouni Maryam , Riviere Michael , Leighton Anna , Peters Melissa , Chowdhury Shimul , Volkmuth Wayne , Levy Samuel 
Published: January 2024

Abstract
Background: Pancreatic cystic lesions are common incidental findings on imaging, but up to half may be precursors of pancreatic cancer. Current diagnostic methods cannot robustly identify cysts that have the highest probability to progress to cancer and require treatment. To address this gap, we evaluated the performance of a non-invasive epigenomic based test employing cell-free DNA, the Avantect Pancreatic Cancer test, in a cohort of patients with pancreatic cysts to identify those at higher risk of malignancy. Methods: In this study, we investigated the use of Avantect in a cohort of patients with pancreatic cysts. Whole blood was collected from 44 patients with cysts: 18 patients with high/moderate and 26 patients with low grade dysplasia/benign cysts. In parallel, demographic information, imaging results, surgical reports, and histological findings were collected for analysis and clinical annotation of patients. Results: Avantect was successfully run on all 44 pancreatic cysts. 16 out of the 18 (89%) patients with cysts of moderate/high grade dysplasia were detected having an abnormal pancreatic signal associated with pancreatic cancer. Of the 26 patients with cysts with low grade/benign features 8 (31%) were detected by Avantect as abnormal. This nearly three-fold higher detection rate for abnormal pancreatic signals in patients with cysts with medium/high grade dysplasia suggests the detection of epigenomic changes as precursors to pancreatic cancer. Conclusions: The Avantect Pancreatic Cancer test shows initial promise in distinguishing between low grade/benign and moderate/high grade dysplasia cysts. Larger studies have been commenced to enable prospective evaluation of Avantect for the management and surveillance of individuals with pancreatic cysts.
Citation Format: Anna Bergamaschi, David Haan, Verena Friedl, Gulfem Guler, Michael Kesling, Micah Collins, Kyle Hazen, Vanessa Lopez, Roger Malta, Maryam Nabiyouni, Michael Riviere, Anna Leighton, Melissa Peters, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy. Evaluation of the Avantect Pancreatic Cancer Test for identifying high-risk pancreatic cysts [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A010.
Abstract A013: Uptake and predictors of Covid-19 vaccination among United States’ cancer populations
Authors: Greene Tayla , Olaosebikan Kikelomo , Idolor Osahon , Appiah-Pippim James 
Published: January 2024

Abstract
The COVID-19 pandemic led different stakeholders to call for measures to reduce the morbidity and mortality associated with it. However, following the development of a vaccine, United States adults were reluctant to get vaccinated against COVID-19. Our objective was to evaluate the uptake of COVID-19 vaccination among at risk adults with cancer, and to analyze the predictors of vaccination. Using 2021 data from the National Health Interview Survey, COVID-19 vaccination uptake among 2703 respondents representing 150 million United States adults with any type of cancer was explored, as well as the sociodemographic and comorbid predictors of the vaccination. Chi-square analysis was used to analyze differences between the vaccinated and unvaccinated respondents, and a multiple logistic regression analysis was used to determine the predictors of COVID-19 vaccination. Among 2703 respondents with any type of cancer, 2317 (83.8%) of them reported vaccination against COVID-19. As compared to those who were unvaccinated, those who were vaccinated were mostly 65+ years and above (88.7% vs 11.4%), females (81.9% vs 18.1%), whites (84.0% vs 16.0%), insured (84.7% vs 15.3%), and educated (92.0% vs 8.0%). With regards to the sociodemographic and comorbid predictors of COVID-19 vaccination. As compared to those less than 40 years of age, those between 40-64 years (AOR 2.55, CI 1.45 – 4.48; p=0.001) and 65 years and above (AOR 4.82, CI 2.65 – 8.79; p=&lt;.001) were more likely to be vaccinated, the insured were more likely be vaccinated as compared to the uninsured (AOR 2.85, CI 1.42 – 5.71; p=0.003), and those who were educated were more likely to be vaccinated (AOR 3.10, CI 2.22 - 4.32; p=&lt;.001) as compared to those who were uneducated. However, being a current smoker of cigarettes was associated with reduced odds of being vaccinated against COVID-19 infection compared to non-smokers (AOR 0.67, 0.47 – 0.97; p=0.035) While there appears to be a reasonable uptake of the COVID-19 vaccine among US adults with any type of cancer, efforts are needed to increase vaccine uptake among those who smoke cigarettes. In addition, younger, uninsured, and less educated adults with any type of cancer may be at a higher risk of contracting COVID-19 infection, and therefore measures to increase uptake in these groups are also.
Citation Format: Tayla Greene, Kikelomo Olaosebikan, Osahon Idolor, James Appiah-Pippim. Uptake and predictors of Covid-19 vaccination among United States’ cancer populations [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A013.
Abstract A020: Molecular basis of immune suppressive microenvironment specified by cancer-associated fibroblasts in pancreatic cancer
Authors: Aoki Kazunori , Fukuda Hironori , Hashimoto Eri , Arai Kosuke 
Published: January 2024

Abstract
Despite constant efforts to improve treatment, the prognosis remains poor, with an overall survival rate of 6% (ranges from 2% to 9%) due to lack of efficient chemotherapy, radiotherapy, and targeted therapy. Immune checkpoint inhibitors (ICIs) has been reported to be effective in various solid cancers, such as melanoma, lung cancer, and renal cell carcinoma. However, pancreatic ductal adenocarcinoma (PDAC) is resistant against ICIs. The responsiveness of immune therapy is mainly determined by immune tumor microenvironment (TME) composed of tumor-infiltrating lymphocytes (TIL) and stromal cells. PDAC possesses unique TME, which is abundant of fibrosis, termed of desmoplasia, and the role of fibrosis in constructing immune suppressive TME remains unclear. First, in this study, to examine the immunological characteristics of TME, we constructed an integrated data base of TIL profiling, RNA-seq and whole exome seq using 31 fresh resected tissues of PDAC. An unsupervised clustering of based on numbers and percentages of 12 TIL types analyzed by flow cytometry showed that PDAC was divided into 2 types of cluster (myeloid cell-, T cell-dominant type), and the prognosis of myeloid type was significantly poorer than T cell-type. Myeloid type contained the high frequency of myeloid cell lineage including monocytes, macrophages and myeloid-derived suppressor cells (MDSC). Only MDSCs were significantly associated with poor prognosis among various immune cell types. Furthermore, gene enrichment analysis identified activated and suppressed pathways in each immune type, and the immune-related pathways were significantly down-regulated in myeloid cell-dominant type. Then, to understand the characteristics of MDSCs infiltrated into pancreatic cancer tissues, single cell RNA-seq with surgical specimens was performed, and the analysis showed that a specific subtype of MDSCs infiltrated into cancer tissues. In addition, activation status of cancer-associated fibroblasts (CAFs) was related with MDSC recruitment and activation, indicating that the interaction between MDSCs and CAFs is crucial to create MDSC-rich TME. Inhibition of interaction between MDSCs and CAFs is expected to overcome immunosuppressive TME can be a novel immunotherapy in PDAC.
Citation Format: Kazunori Aoki, Hironori Fukuda, Eri Hashimoto, Kosuke Arai. Molecular basis of immune suppressive microenvironment specified by cancer-associated fibroblasts in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A020.
Abstract A022: Novel nanoparticle delivery of toll like receptor agonists alters the tumor immune landscape and improves response to standard of care therapy in preclinical PDAC models
Authors: Beals Nathan , Sorrentino Anthony , Bar-Sagi Dafna 
Published: January 2024

Abstract
The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is becoming an increasingly complex system, driven by the interactions between multiple different cell types. These drivers of cancer progression can suppress local immune responses, promote resistance to therapies, and reinforce a pro-tumorigenic TME. Despite advances in other tumor types with immune checkpoint blockade, minimal progress has been made in the treatment of PDAC with immunotherapies targeted at adaptive responses. As such, with a majority of the TME being made up of innate immune cells being skewed towards immunosuppressive phenotypes, there remains an underutilized immunologic target. Of the potential subset of targets, toll like receptors (TLR) have garnered significant interest given the key role they have in controlling the innate immune response in a number of different immune cells. On their own, agonists of these family of receptors lack efficacy, either through poor tumor penetration, lack of target specificity or toxicity. To address this unmet need, we have developed a nano-delivery approach for TLR agonists for target immune cell uptake. Thus far, we have established two conjugates, a protein-based nanoparticle termed FN-TLR7 for the delivery of a CL307-based conjugate and a DNA nanoparticle termed CAGE-TLR9 for the delivery of a CpG-based agonist. We have found that these conjugates can activate target immune cells within the TME via an advantageous pharmacokinetic profile which significantly reduces nonspecific toxicities compared to free agonists. When paired with the current standard of care options in PDAC, we see significant improvements in tumor control. The implications of nano-delivery of TLR agonists for treating PDAC tumors will be discussed.
Citation Format: Nathan Beals, Anthony Sorrentino, Dafna Bar-Sagi. Novel nanoparticle delivery of toll like receptor agonists alters the tumor immune landscape and improves response to standard of care therapy in preclinical PDAC models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A022.
Abstract A024: B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma
Authors: Bertocchi Alice , Hoffman Megan T. , Qiang Li , Hsu Lauren , Dougan Michael , Agudo Judith , Dougan Stephanie K. 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate. Several factors contribute to its dismal prognosis, including resistance to available therapies and high invasiveness. Lymph nodes act as an early systemic source of circulating malignant cells in PDAC, allowing their dissemination to other organs early in disease progression. Lymphatic colonization is linked to worse prognosis. Therefore, a better understanding of mechanisms regulating lymph node metastasis is clinically needed. To study each step in the metastatic cascade to the lymph nodes, we have developed a mouse co-clinical model of resectable pancreatic cancer. This model consists of subcutaneous injection of highly metastatic pancreatic cancer cells, followed by surgical resection of the primary tumor. Following resection, mice spontaneously develop lymph nodes metastasis at a comparable frequency to human PDAC post-surgical recurrence, on a similar time scale relative to the lifespans of mice and humans. Expression of nuclear tdTomato allows detection of single cancer cells seeding the draining lymph nodes early in disease progression, even before metastases are histological detectable. Using this model, we are gaining insights into the first steps of metastatic seeding of lymph nodes, and have identified a pro-metastatic role for B cells. These findings will enhance our understanding of lymphatic colonization in PDAC and potentially inform immunotherapeutic interventions to disrupt the metastatic cascade.
Citation Format: Alice Bertocchi, Megan T. Hoffman, Li Qiang, Lauren Hsu, Michael Dougan, Judith Agudo, Stephanie K. Dougan. B cells facilitate lymph node colonization in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A024.
Abstract A031: Biotherapeutic strategies targeting the CXCR2 axis for depletion of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma
Authors: Christopher Benjamin N. , Reyes Lety , Robinson Reeder , Golick Lena , Dolloff Nathan 
Published: January 2024

Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) has a 5-year survival rate of only 10%, and limited treatment options exist. Immune checkpoint inhibitors are effective in a variety of cancer types; however, the complex immunosuppressive tumor microenvironment (TME) of PDAC is a significant barrier to immunotherapy. Myeloid-derived suppressor cells (MDSCs) are abundant in PDAC tumors from humans and mouse models. MDSCs suppress effector T cell function and promote the expansion of other immunosuppressive cell types. This led us to hypothesize that targeting tumor MDSCs would be an effective therapeutic strategy for PDAC and enhance the efficacy of T cell based immunotherapy. Our preliminary data and the work from others shows that CXCR2 ligands such as CXCL8/IL-8, CXCL5/ENA78, and CXCL1/GROα are the most abundant soluble factors secreted by PDAC cells. CXCR2 ligands are critical for the homing of myeloid cells to sites of injury in cutaneous wound healing, suggesting that dysregulated secretion of CXCR2 chemokines in PDAC may mimic a wound healing response that attracts myeloid cells and promotes the expansion of MDSCs and an immunosuppressive TME. To test this hypothesis, we have designed and produced multiple drug-conjugated CXCR2 ligand-based engineered proteins to target and eliminate MDSCs from PDAC tumors. We are referring to these novel biotherapeutic molecules as Ligand Drug Conjugates (LDCs). We have demonstrated binding, internalization, induction of signaling, and cytotoxicity of these LDCs to CXCR2 expressing myeloid cells. Our data suggests that our engineered proteins are superior binders and activators of CXCR2 axis signaling compared to WT CXCR2 ligands. Utilizing CXCR2 knockin models we demonstrated that the cytotoxicity of our LDCs is CXCR2 dependent. In vivo, we are utilizing the KPC (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre) mouse model of PDAC, which we've shown in preliminary studies to, like human PDAC, support an abundance of MDSCs in tumors as well as secondary lymphoid organs such as the spleen. We anticipate that this study will demonstrate the therapeutic potential and actionability of targeting MDSCs and will provide novel biotherapeutic drug candidates that will ultimately improve immunotherapy outcomes in patients with PDAC.
Citation Format: Benjamin N. Christopher, Lety Reyes, Reeder Robinson, Lena Golick, Nathan Dolloff. Biotherapeutic strategies targeting the CXCR2 axis for depletion of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A031.
Abstract A033: Blocking TNF-a producing macrophage activates antitumor immunity in pancreatic cancer via IL33
Authors: Dixit Ajay , Provenzano Paolo , Sarver Aaron , Zettervall Jon , Huang Huocong , Zheng Kexin , Brekken Rolf 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDA) remains resistant to immune therapies, largely due to robustly fibrotic and immunosuppressive tumor microenvironments. It has been postulated that excessive accumulation of immunosuppressive myeloid cells influences immunotherapy resistance and recent studies targeting macrophages in combination with checkpoint blockade have demonstrated promising preclinical results. Yet, our understanding of tumor-associated macrophage (TAM) function, complexity, and diversity in PDA remains limited. Here, analysis of human PDA single cell sequencing data revealed significant macrophage heterogeneity, with bone marrow-derived monocytes serving as the primary source for immunosuppressive TAMs. These bone marrow derived macrophages also served as a primary source of TNF-a. Deletion of Ccr2 in genetically engineered KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) mice decreased monocyte recruitment resulting in decreased metastasis, and increased survival. Moreover, intervention studies targeting CCR2 with a new orthosteric inhibitor (CCX598) renders PDA susceptible to checkpoint blockade therapy (CTLA-4 and PD-L1) resulting in reduced metastatic burden and increased survival in KPC mice. Additionally, TNF-a suppresses the expression of alarmin IL-33 in cancer cells, thereby hindering dendritic cell and cytotoxic T cell anti-tumor activity. When put together our data indicate that interventions to disrupt infiltration of immunosuppressive macrophages lead to decreased TNF-a, decreased metastasis and increased survival in two different models suggesting its potential role to overcome barriers to effective immunotherapeutics for PDA.
Citation Format: Ajay Dixit, Paolo Provenzano, Aaron Sarver, Jon Zettervall, Huocong Huang, Kexin Zheng, Rolf Brekken. Blocking TNF-a producing macrophage activates antitumor immunity in pancreatic cancer via IL33 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A033.
Abstract A058: Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis
Authors: Chen Ziheng , Ho I-Lin , Draetta Giulio , Ying Haoqiang 
Published: January 2024

Abstract
Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The essential contributions of mitochondrial metabolism to fuel tumor growth and resistance to therapy are now evident in multiple contexts. However, targeting of mitochondrial metabolism in the clinical setting has repeatedly failed, owing to a narrow therapeutic window and the remarkable ability of tumor cells to activate compensatory metabolic programs. Thus, it is essential to uncover additional mechanisms that may render cancer cells selectively susceptible to treatment and those that enable them to survive when exposed to mitochondrial metabolism-targeted drugs. Here, using pancreatic ductal adenocarcinoma (PDAC) as a disease model, we report that cellular and, in particular, mitochondrial lipid composition affects the sensitivity of cancer cells to pharmacological inhibition of electron transport chain complex I. Metabolomic, including lipidomic, analyses of patient-derived PDAC models uncovered a critical role for monosaturated fatty acids (MUFAs) and demonstrated that MUFA-linked ether phospholipids have a critical role to sustain homeostasis of mitochondrial reactive oxygen species (ROS). Blocking de novo ether phospholipid biosynthesis in the peroxisomes, sensitized PDAC cells to mitochondrial complex I inhibition by inducing mitochondrial ROS and lipid peroxidation. Biochemical analysis revealed a role of ether phospholipids in the assembly of mitochondrial supercomplexes and ROS production. Together, our data identify an ether phospholipid-dependent mechanism that regulates mitochondrial redox control and contributes to the sensitivity of PDAC cells to complex I inhibition. These findings might lead to novel approaches to target mitochondrial metabolism in cancer cells.
Citation Format: Ziheng Chen, I-Lin Ho, Giulio Draetta, Haoqiang Ying. Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A058.
Abstract A069: Study of MUC16/ERBB axis in pancreatic cancer
Authors: Baniya Amina , Hollingsworth Michael A. (Tony) 
Published: January 2024

Abstract
Background: Pancreatic cancer is the third leading cause of cancer-related deaths due to its poor prognosis and highly malignant nature. The altered expression of glycans and glycoproteins is associated with malignancy. MUC16 (also known as CA125) is a member of mucin family of glycoproteins known to line epithelial cells for protection and lubrication and is overexpressed in several cancer types, including pancreatic cancer, often linked with enhanced disease progression, metastasis, and reduced patient survival. Significance: Circulating levels of MUC16/CA125 has been used as a biomarker to monitor adenocarcinoma for decades. However, the functional role of CA125/MUC16 is yet to be elucidated due to a lack of studies on its large, heavily glycosylated structure and unknown functional domains. We present evidence that in addition to serving as a biomarker, circulating MUC16 has pro-tumorigenic activities. Hypothesis: Based on recent findings, we hypothesize that isoforms of MUC16 have high avidity for ErbB receptor and integrin complexes, with concomitant activation of downstream signaling cascades that include Akt and FAK, respectively. These result in the increased tumorigenic potential of pancreatic cancer cells in an autocrine manner. Experimental Design: There are four members of ErbB receptors; where receptor dimerization is a function of ligand binding and results in distinct downstream oncogenic signaling cascades. We evaluated the binding of MUC16 to different ErbB receptors, and its capacity to activate downstream signaling pathways using pancreatic cell line models that have different combinations of knock out/down of each ErbB receptor. We evaluated the global changes in the phosphorylation of oncogenic signaling molecules due to MUC16 binding using Reverse Phase Protein Array (RPPA). Results: We found that MUC16 activates Erbb4 (Y1162) along with other members of ErbB receptor family, where glycosylation of MUC16 is crucial for its biological activity. MUC16 enhanced oncogenic signaling through the phosphorylation of various downstream molecules and activated PI3K, RTK, MAPK, and DNA repair pathways. Our future directions include elucidating the molecular mechanism by which MUC16 activates the oncogenic signaling cascades via binding to ErbB receptors using our pancreatic cell line-based models. Conclusions: Understanding the biological activity of MUC16 and its cleaved product will further help in investigating the role of MUC16 in tumor microenvironment and at distant organ sites to influence the metastatic niche.
Citation Format: Amina Baniya, Michael A. (Tony) Hollingsworth. Study of MUC16/ERBB axis in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A069.