tbuckley/cabot-search huggingface dataset:
Abstract 6445: Exploring the relationship between PSCA and PD-L1 by a comprehensive tumor immunohistochemical analysis
Authors: Yichen Guo, Rachel Gonzalez, Jina Yom, Bailey Gilmore, Tianli Qu, Xiaomin Hu, Andy (Xi) Han, Zhaoying Guo, Eden Zewdu, Xuan Liu, Wei Fu
Journal: Cancer Research (2024)

Abstract Prostate Stem Cell Antigen (PSCA) is a well-established diagnostic marker in various cancers and a promising target for immunotherapy. Programmed Death-Ligand 1 (PD-L1) plays a crucial role in cancer immune regulation and is known to influence patient response to checkpoint inhibitors. The objective of this study is to elucidate the relationship between PSCA and PD-L1 in diverse cancer types and to provide valuable insights for the development of an effective immunotherapy strategy. To accomplish this, immunohistochemical (IHC) analysis was conducted on paraffin-embedded Cytosections obtained from 20 lung cancers, 20 prostate cancers, 32 bladder cancers, and 20 normal tissues for each respective cancer type. Antibodies generated by Origene were utilized to detect the expression of PSCA and PD-L1 on the cell surface. The IHC results of tumor tissue were standardized against corresponding normal samples, and the correlation between these two genes was statistically analyzed using analysis of variance (ANOVA). The findings reveal a significant positive correlation between the expression of PSCA and PD-L1 (r=+0.78, P=0.016), suggesting an underlying mechanism driving their co-expression in the studied cancers. Understanding PSCA and PD-L1 coexpression in bladder, lung, and prostate cancers has great potential for informing tailored immunotherapies. Future research should explore functional consequences within the tumor microenvironment, advancing precision immunotherapy for improved outcomes in these challenging malignancies. Citation Format: Yichen Guo, Rachel Gonzalez, Jina Yom, Bailey Gilmore, Tianli Qu, Xiaomin Hu, Andy (Xi) Han, Zhaoying Guo, Eden Zewdu, Xuan Liu, Wei Fu. Exploring the relationship between PSCA and PD-L1 by a comprehensive tumor immunohistochemical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6445.
Abstract 6462: Somatic mutational profile in MUTYH- associated colorectal cancers (MUTYH-CRCs)
Authors: David Kaldas, Tiago Biachi de Castria
Journal: Cancer Research (2024)

Abstract Background: Biallelic inactivation of MUTYH leads to hereditary predisposition to colorectal polyposis and CRC. Herein we evaluated co-alterations in somatic next-generation sequencing (NGS) in patients with MUTYH-CRC, mainly KRAS G12C, high tumor mutational burden and microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR). Methods: Data was collected on patients with MUTYH-CRC in the period between 2015 and 2023 at Moffitt Cancer Center (Tampa, Florida, United States). All patients with MUTYH-CRC were included regardless disease stage. Different germline panels were used to detect MUTYH and Foundation One, Caris and Moffitt STAR (in house NGS) were used to detect somatic co-alterations. Results: A total of 36 patients were identified with MUTYH- CRC, the median age at diagnosis was 44-year-old, 55% were men. All patients had a somatic NGS available, 18 patients (50%) had KRAS mutation, and specifically KRAS G12C was detected in 9 patients (24%), 6 patients (17%) had MSI-H/dMMR, 5 patients (14%) had BRAF mutation and 4 patients (11%) with BRCA2 mutation. Conclusion: MUTYH-CRC is associated with a high incidence of targetable alterations including KRAS G12C and BRAF. Considering unique characteristics in MUTYH-CRC tumor microenvironment, including T cell infiltrate, trials combining KRAS G12C/BRAF inhibitors and immune checkpoint inhibitors are warranted. Citation Format: David Kaldas, Tiago Biachi de Castria. Somatic mutational profile in MUTYH- associated colorectal cancers (MUTYH-CRCs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6462.
Abstract 6533: Pivotal role of specific LYVE1+ tissue resident macrophages in PDAC progression &amp; immunotherapy resistance
Authors: Hong Li, Jun Yan
Journal: Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense fibrotic stroma and abundant myeloid cell infiltration, which render it resistant to any therapeutic interventions, including immunocheckpoint blockade (ICB) therapy. Understanding the composition and function of myeloid cells within the PDAC microenvironment may help identify promising targets for PDAC immunotherapy. Tissue resident macrophages (TRMs) contribute to organogenesis and tissue regeneration and metabolism. In this study, we discovered a distinct population of pancreas TRMs that highly express lymphatic vessel hyaluronan receptor 1 (LYVE-1). Single cell RNAseq data reveal that LYVE-1+ TRM cluster in the pancreas expresses high levels of complement activation genes and transcription factors such as c-Maf and Stab1. RNAseq data also confirm that LYVE-1+ TRMs express enriched genes related to mannose binding, endocytosis, and glutathione metabolic process, while LYVE-1 negative macrophages express enriched genes related to antigen processing and presentation, T cell activation, and phagocytosis. Multiparameter flow cytometric analysis demonstrates that LYVE-1+ TRMs express M2-like markers, including increased CD163, CD206 and decreased MHC Class II molecule. During PDAC development and progression, LYVE-1+ TRMs expand and localize around the tumor border, promoting fibrotic stroma formation. Imaging mass cytometry (IMC) also reveals abundant infiltration of LYVE-1+CD14+CD68+ macrophages in human PDAC tumors and colocalized with collagen deposition. This subset of macrophages also highly express c-Maf. Through the use of Lys-Cre-c-Maf f/f mice, we demonstrate that depletion of c-Maf from myeloid cells significantly reduces LYVE-1+ TRMs and polarizes them to resemble an M1-like phenotype. In conclusion, our findings suggest that LYVE-1+ macrophages are a unique subset of myeloid cells within the pancreas and likely play a critical role in PDAC progression and immunotherapeutic resistance. Future work will focus on targeting LYVE1+ TRMs using various approaches, such as conditional knockout mice and small molecule inhibitors, to determine their therapeutic potential for PDAC treatment. Presented by Dr. Hong Li Citation Format: Hong Li, Jun Yan. Pivotal role of specific LYVE1+ tissue resident macrophages in PDAC progression &amp; immunotherapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6533.
Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study
Authors: Michelle Ylade, Maria Vinna Crisostomo, Jedas Veronica Daag, Kristal An Agrupis, Anna Maureen Cuachin, Ava Kristy Sy, Deok Ryun Kim, Hyeon Seon Ahn, Ana Coello Escoto, Leah C Katzelnick, Cameron Adams, Laura White, Aravinda M de Silva, Jacqueline Deen, Anna Lena Lopez
Journal: The Lancet Infectious Diseases (2024)

BackgroundA three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections.MethodsIn this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9–14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline.FindingsA single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20–88; p=0·017) and the entire follow-up period (67%, 19–87; p=0·016).InterpretationThe risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines.FundingThe Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases.
Abstract 80: Toward best practices for B-cell receptor repertoire profiling
Authors: Wenming Xiao
Journal: Cancer Research (2024)

Abstract FDA anticipates that immune cell receptor profiling will become crucial to the Agency’s evaluation of the efficacy and safety of emerging cancer immunotherapies and immunomodulatory drugs by advancing precision medicine and providing orthogonal, functional evidence. High-throughput sequencing of B-cell receptor sequencing (BCR) gene rearrangements and downstream analysis empowers researchers to define the B-cell clonal landscape, as well as identify biomarkers for minimal residual disease (MRD). Although this field has made vast strides over the last decade, it lacks standardized assay controls, adequate sensitivity and specificity in gene mapping/alignment, and appropriately qualified reference data sets, materials, and validation methods. Moreover, detailed comparisons of wet-bench analytical methods or bioinformatic procedures have not appeared. The FDA led B-cell receptor sequencing quality control (BCR-SEQC) consortium is establishing protocols for the development of reference materials and data sets for the evaluation of NGS-based BCR repertoire reconstruction. The consortium is also developing materials for performance bench-marking studies. To this end, we performed whole-genome sequencing, RNAseq, and BCR-seq on 50 B-cell lines to determine the clonotype, full-length transcripts, and expression abundance of BCR genes in each cell line. Two batches of reference materials (DNA, RNA, and cells) were generated from each of nine cell lines that were determined unambiguously to be monoclonal in BCR expression of both heavy and light chains. These materials were distributed to ten companies to test up to 15 BCR-seq products. Our benchmarking studies include six widely-used sequencing technologies. The overarching objectives of this research were to elucidate current capabilities and limitations, address fundamental technical needs, provide reference materials and data sets, and establish actionable best practices for reconstructing B cell receptor repertoires from NGS data. Citation Format: Wenming Xiao, BCR-SEQC consortium. Toward best practices for B-cell receptor repertoire profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 80.
Abstract 802: Molecular profile of gastric cancer in Hispanics living in Puerto Rico
Authors: Ingrid Montes-Rodriguez, Hilmaris Centeno-Girona, Noridza Rivera, Marcia Cruz-Correa
Journal: Cancer Research (2024)

Abstract Gastric cancer (GC) is the 4th leading cause of cancer death globally. The incidence and mortality rates of GC differ dramatically between racial/ethnic groupings. In the United States (U.S.), Hispanics, non-Hispanic Blacks, and Asian or Pacific Islanders are more likely to be diagnosed with GC and have a higher mortality rate than non-Hispanic Whites. Among the Hispanic population living in Puerto Rico (PRH), GC ranks among the top ten leading causes of cancer death, whereas this malignancy is not a major cause of cancer mortality in the mainland U.S. Tumor profiling approaches have resulted in the discovery of actionable gene alterations, which serve as a guide for treatment strategies and ultimately enhance the overall survival rates of individuals diagnosed with cancer. However, descriptive information regarding the genetic mutational landscape of GC tumors from PRH is limited. This study aims to describe the genomic profile of GC tumors in PRH and to identify the most prevalent genetic mutations. We retrospectively examined GC tumor mutational profiles from 106 PRH that underwent NGS testing from 2015 to 2022 (provided by CARIS Life Sciences and the Precision Oncology Alliance). We compared PRH GC tumor somatic mutation prevalence to TCGA and the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE), both available through the cBioPortal for Cancer Genomics. Descriptive statistics were performed to characterize the database. Among the top mutated genes for GC tumors in PRH were TP53 (54.1%, n=85), ARID1A (34.2%, n=73), KMT2D (30.5%, n=82), CDH1 (29.4%, n=85) and ZFHX3 (27.3%, n=55). The most frequent gene amplifications were ERBB2 (7.1%, n=84), KRAS (6.0%, n=84), and CCNE1 (4.9%, n=81). Compared to other datasets, PRH had significantly different mutational frequencies of GC driver genes like TP53, ARID1A, CDH1, and KMT2D. This study is the first to report PRH GC tumor mutational profiles and compare the mutational frequencies to other non-Hispanic and U.S. mainland Hispanic populations using TCGA and GENIE data sets. Furthermore, our study provides data on the specific mutational landscape for Hispanics with GC and the implications on therapeutic options and clinical outcomes. Developing new treatments for genomically diverse populations requires understanding the most common carcinogenic molecular pathways that affect Hispanics with GC. Citation Format: Ingrid Montes-Rodriguez, Hilmaris Centeno-Girona, Noridza Rivera, Marcia Cruz-Correa. Molecular profile of gastric cancer in Hispanics living in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 802.
Abstract 798: Increasing breast cancer incidence across generation status in Mexican American women: The Multiethnic Cohort
Authors: Xinman Zhang, Iona Cheng, Adelynn Paik, Brian Huang, Veronica Wendy Setiawan
Journal: Cancer Research (2024)

Abstract Background: Breast cancer (BC) is the most commonly diagnosed cancer among Latino women in the US. Compared to foreign-born Latino women, US-born Latino women have a higher incidence of BC. While prior studies have suggested this difference in incidence may be explained by risk factors such as unhealthy lifestyle behaviors, reproductive history, and neighborhood socioeconomic status, it is unclear how the risk of BC has changed over generations among Latinos women. In this study, we investigated the association between generational status and BC incidence among Mexican American women within the Multiethnic Cohort (MEC). Methods: The study population included 15,303 self-reported Mexican Americans from the MEC. Generational status was categorized as: 1st generation (Mexico-born, n = 6,347), 2nd generation (US-born with one or two parents born in Mexico, n = 6,390), or 3rd generation (US-born with both parents born in the US, n = 2,566). Multivariable Cox models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of BC incidence by generational status. All models were adjusted for relevant risk factors including age, physical activity, smoking, alcohol intake, education, body mass index, diet, family history of BC, menopausal status, age at menarche, parity, mammography history, hormone use, neighborhood socioeconomic status, and Hispanic ethnic enclave. Results: During an average 21.5-year follow-up, 815 incident BC cases were identified. The age-adjusted incidence rate (per 100,000) of BC increased by generation (1st: 191.9; 2nd: 265.3; 3rd: 284.0). Third (70.4%) and 2nd (66.5%) generations had a larger proportion of localized disease at diagnosis compared to 1st generation women (59.7%). Compared to 1st generation Mexican Americans, 2nd (HR = 1.24; 95% CI: 1.03-1.49) and 3rd generation (HR = 1.28; 95% CI: 1.02-1.60) had elevated risks of BC (p-trend: 0.02) The positive association with generational status remained significant when restricting to women who reported mammogram use (HR 2nd vs. 1st = 1.27, 95% CI: 1.04-1.55; HR 3rd vs. 1st = 1.34, 95% CI: 1.06-1.70) (p-trend: 0.01). Conclusions: Our findings suggest that generational status among Mexican American women is associated with risk of BC, after adjusting for sociodemographic, lifestyle, neighborhood, and reproductive risk factors. Further studies are warranted to discover the potential factors that contribute to this increased risk and elucidate the underlying etiology. Citation Format: Xinman Zhang, Iona Cheng, Adelynn Paik, Brian Huang, Veronica Wendy Setiawan. Increasing breast cancer incidence across generation status in Mexican American women: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 798.
Abstract 7636: Quantitative analysis of colorectal adenocarcinoma images obtained by single-shot 17-plex staining followed by imaging with the Orion™ spatial biology platform
Authors: Edward Lo, Tad George, Selena Larkin
Journal: Cancer Research (2024)

Abstract Background To understand the tumor microenvironment (TME), high resolution imaging of multiple biomarkers with whole slide context can be used as a basis for downstream biomarker quantitation and predicting patient outcomes1. Here we investigate a sample of invasive colorectal adenocarcinoma using whole slide, single-step high-plex staining and imaging at single-cell resolution followed by quantitative analysis. Methods The slide was stained in one round with a 17-plex immune-oncology panel then imaged in one round with the Orion™ spatial biology platform. Quantitative analysis was performed on the resulting TIFF file using the following pipeline:- Manually annotate regions of interest (ROI) on the tissue- Segment whole slide images into cells with UnMICST and S3segmenter - Import mask and clean data in QuPath - Generate primary feature data table with QuPath - Classify cells into populations in QuPath - Generate spatial biomarkers - Compare cell populations and their spatial interactions in the different ROIs. Results Data revealed a distinction between normal colonic epithelium, well-differentiated adenocarcinoma with immune cell collection, and an infiltrating border of the carcinoma. Differences in immune cell content and spatial organization were measured, and the infiltrating border found to contrast with other tumor regions by showing a lower proliferative fraction (Ki-67, nuclear) and differences in E-cadherin and cytokeratin expression patterns. Conclusions These data highlight the importance of sufficient plex, resolution and whole slide context to derive reliable spatial biomarkers of potential prognostic value. Further, hours vs. days speed for whole-section multiplexed biomarker quantitation, along with same-section conventional chromogenic analysis, makes this approach suited to multi-patient clinical studies. 1 JR Lin et al., High-plex immunofluorescence imaging and traditional histology of the same tissue section for discovering image-based biomarkers, Nat Cancer, 4, 1036-1052 (2023). Citation Format: Edward Lo, Tad George, Selena Larkin. Quantitative analysis of colorectal adenocarcinoma images obtained by single-shot 17-plex staining followed by imaging with the Orion™ spatial biology platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7636.
Abstract 504: Anticancer effects of kaempferol through cell cycle arrest and the inhibition of proliferation in genetically distinct triple-negative breast cancer cells
Authors: Sukhmandeep Kaur, Patricia Mendonca, Karam F. A. Soliman
Journal: Cancer Research (2024)

Abstract Triple-negative breast cancer (TNBC) is one of the most known aggressive subtypes of breast cancer, affecting 1 in 3 newly diagnosed cancers in women. TNBC affects African-American women disproportionally in comparison to Caucasian women. Due to the lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER-2), it poses direct challenges to the efficacy of standard hormonal therapies. The current TNBC treatments present higher toxicity and multiple side effects. An alternative would be using natural compounds that have emerged as potential anticancer agents. Kaempferol is a major flavonoid aglycone found in many fruits, vegetables, and herbs, including grapes, tomatoes, broccoli, tea, and ginkgo biloba leaves. In this study, we investigated the differential effect of kaempferol on cell toxicity, cell growth, and underlying mechanisms in inducing cell cycle arrest in genetically different TNBC cells from Caucasian (MDA-MB-231) and African American (MDA-MB- 468) women. Kaempferol significantly inhibited cell growth in both the cell lines with a more profound effect against MDA-MB-231 (IC50: 43.86 µM) compared to MDA-MB-468 cells (IC50: 53.47 µM). Also, kaempferol treatment induced cell cycle arrest at S-phase in both cancer cell subtypes. The MDA-MB-231 cells showed a kaempferol effect at lower concentrations (6.25µM and 12.5µM), while MDA-MB-468 cells showed the same effect at higher concentrations (25µM and 50µM). Kaempferol also modulated CDK gene expression associated with cell cycle progression in breast cancer cells. The inhibition at S-phase is important in cancer treatment because it targets the highly proliferative nature of cancer cells characterized by uncontrolled cell division. This study indicates that, by inducing cell cycle arrest at the S-phase, kaempferol may interfere with cancer cell growth and proliferation by inhibiting DNA replication, offering potential therapeutic benefits. This approach could reduce side effects and increase treatment efficacy, providing hope for more effective interventions in the fight against TNBC. Citation Format: Sukhmandeep Kaur, Patricia Mendonca, Karam F. A. Soliman. Anticancer effects of kaempferol through cell cycle arrest and the inhibition of proliferation in genetically distinct triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 504.