tbuckley/cabot-search huggingface dataset:
Abstract 693: Comparative gene signature between NEPC and CRPC transcriptomics
Authors: Srinivas V. Koduru, Mark Kidd, Abdel Halim
Journal: Cancer Research (2025)

Abstract Introduction: Prostate cancer (PCa) is the most common cancer in men, with an estimated 299, 010 new cases and 32, 250 deaths projected in 2024. Approximately 1 in 8 men will be diagnosed with PCa, with the majority (60%) occurring in those aged 65 or older. Castration-resistant prostate cancer (CRPC) represents an advanced stage of PCa, with up to 30% of these cases classified as neuroendocrine prostate cancer (NEPC). Previous studies have demonstrated that DNA methylation, chromatin integrity, and transcriptional regulation play crucial roles in the development of treatment-resistant PCa. In this study, we aim to apply next-generation sequencing (NGS) to identify gene signatures regulated in CRPC and NEPC using whole blood samples from patients to discover circulating RNAs and their dysregulated pathways. Methods: Whole blood samples were collected from NEPC (n=9), CRPC (n=5), and healthy controls (n=11). Total RNA was extracted using TRIzol and RNeasy kits, with quality control assessed via Bioanalyzer. RNA-seq was performed on a NovaSeq 6000 platform, and data were analyzed using PartekFlow with High Performance computing system (HPC) to identify differential gene expression patterns. Pathway analysis was conducted on the differentially expressed genes. Results: RNA-seq analysis revealed significant differences in gene expression between NEPC, CRPC, and healthy controls. In total, 4, 655 genes were found to be significantly differentially expressed (fold change &amp;gt;1; P&amp;lt;0.05) in NEPC, and 2, 944 genes in CRPC. Notably, 28% of the statistically significant genes overlapped between NEPC and CRPC. Additionally, analysis of the Wren's PROSTest (27 genes) and NETest (55 genes) signatures identified 25 and 43 genes in NEPC, and 23 and 41 genes in CRPC, respectively, within the differentially expressed gene sets. Conclusion: Our transcriptomic data reveal that NEPC and CRPC share approximately 28% of their gene signatures, with significant correlation to the PROSTest and NETest gene panels. This highlights the potential of these gene signatures as diagnostic tools in identifying and understanding the progression of advanced prostate cancer. Citation Format: Srinivas V. Koduru, Mark Kidd, Abdel Halim. Comparative gene signature between NEPC and CRPC transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 693.
Abstract 1357: miR-16-5p and miR-124-3p block the immunosuppressive phenotype of GBM cells in vitro
Authors: TC Taylor, Amanda Johnson, Harmon Khela, Jack Korleski, Sophie Sall, Bachchu Lal, Karen Smith-Connor, Hernando Lopez-Bertoni
Journal: Cancer Research (2025)

Abstract A hallmark of GBM is its highly-immunosuppressive tumor microenvironment (TME). GBM stem-like cells (GSCs) can evade immune surveillance to allow for continued tumor growth and propagation. GSCs regulate the immune TME through recruitment and production of immunosuppressive cells and factors via tumor cell-intrinsic mechanisms. Blocking these cell-intrinsic immunosuppressive mechanisms is widely viewed as a way to enhance the effects of current immune therapies. We recently showed that TGFβ type II receptor (TGFBR2) promotes a mesenchymal transition in GBM cells characterized by high expression levels of immunosuppressive genes NT5E (CD73), ENTPD1 (CD73), LGALS1 (galectin-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and TGFB1. miRNA network analysis identified miR-16-5p and miR-124-3p as high-confidence candidates to block the expression of these immunosuppressive signaling axis in GBM cells. Transgenic miR-16-5p and miR-124-3p simultaneously reduced expression of CD274, ENTPD1, NT5E, TGFB1, and LGALS1 and increased tumor cell killing of PBMC-derived CD4+ and CD8+ T cells. We also measured an increase in drivers of the CD8+ effector state and a decrease in expression of exhaustion marker PD1 in PBMC-derived CD8+ T cells. In addition to the effects on CD4+ and CD8+ T cell activation and function, miRNA-mediated knock-down of this immunosuppressive gene signature in tumor cells also resulted in a decrease in CD206 expression and reduced release of anti-inflammatory chemokines in THP1 cells. These findings demonstrate that miRNA-based gene inhibition can block cell-intrinsic immunosuppressive pathways to enhance anti-tumor immune cell function in vitro and predicts that delivering these miRNAs using advanced nanocarriers will cooperate with current immunotherapies in vivo. Citation Format: TC Taylor, Amanda Johnson, Harmon Khela, Jack Korleski, Sophie Sall, Bachchu Lal, Karen Smith-Connor, Hernando Lopez-Bertoni. miR-16-5p and miR-124-3p block the immunosuppressive phenotype of GBM cells in vitro. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1357.
Abstract 1360: Neutrophil extracellular traps establish the pre-metastatic niche in the omentum by expanding innate-like B cells that express IL-10
Authors: WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora
Journal: Cancer Research (2025)

Abstract Disseminated cancer cells in the peritoneal fluid frequently implant on the omentum, an immune cell-rich fatty tissue that drapes from the stomach, but the underlying mechanisms are poorly understood. In this study, we identified that innate-like B cells accumulate in the uninvolved omentum of mice and women with early-stage ovarian cancer concomitantly with the release of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer showed that NETs induce expression of the chemokine CXCL13 in mesothelial cells in the pre-metastatic omentum, stimulating recruitment of innate-like B cells from the peritoneal cavity. Furthermore, studies using IL-10-reporter mice showed that NETs stimulate innate-like B cells to produce IL-10 that in turn expands regulatory T cells in the pre-metastatic omentum and potentiates metastasis at this site. Ex vivo studies showed that NETs elicit IL-10 production in innate-like B cells by generating reactive oxygen species and by inactivating SHP-1, a phosphatase that inhibits B cell activation pathways, through dissociating SHP-1 from CD22. These findings reveal that NETs alter immune cell dynamics in the pre-metastatic omentum and render this niche permissive for cancer cell colonization. Citation Format: WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora. Neutrophil extracellular traps establish the pre-metastatic niche in the omentum by expanding innate-like B cells that express IL-10 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1360.
Abstract 2828: Anthocyanin-induced autophagosome accumulation and mitochondrial dysfunction drive apoptosis in liver cancer cells
Authors: Anyssa Rodriguez, Samantha Tamayo, Aarya Tripathi, Sumeet Chauhan, Subash Chauhan, Nirakar Sahoo
Journal: Cancer Research (2025)

Abstract Introduction: Liver cancer remains one of the most lethal malignancies worldwide. Hepatocellular carcinoma (HCC) accounts for most cases. Existing therapies provide limited efficacy, especially in advanced stages, highlighting the urgent need for alternative treatments. Recent studies have demonstrated that anthocyanins, a natural plant-derived compound, show anticancer potential. Dracorhodin Perchlorate (DP), a synthetic analog of anthocyanin found in Daemonorops draco fruit, exhibits cytotoxic effects in cancer cells. This study investigates the mechanisms underlying DP’s cytotoxicity in HCC. Methods: We examined the effect of DP on human liver cancer cells (SK-HEP1). We employed an integrative experimental approach combining cell viability assay, death pathway analysis, autophagy monitoring, lysosomal function evaluation, oxidative stress assessment, and mitochondrial integrity. Western blot, immunocytochemistry, and live cell imaging were employed. Results: Our result shows that DP significantly reduced SK-HEP1cell viability in a time- and dose-dependent manner. The IC50 values decreased from 60 µM at 24 hours, 26 µM at 48 hours, and 18 µM at 72 hours, reaching 12 µM at 96 hours. We observed decreased pro-caspase-3 levels in DP-treated cells, confirming apoptosis. We found no change in phosphorylated MLKL levels, ruling out necroptosis. Interestingly, we observed a significant increase in LC3II/I ratios and LC3 puncta, indicating autophagosome accumulation. However, we noted no increase in lysosomal activity-based DQ-BSA and Lysotracker assays, suggesting autophagic flux inhibition. Furthermore, we detected a significant rise in reactive oxygen species (ROS) levels following DP treatment, accompanied by elevated HO-1 expression. We found evidence of mitochondrial dysfunction, as Mitotracker assays revealed fragmented mitochondria and reduced cytochrome c release. We observed that Bafilomycin A1 amplified DP-induced apoptosis, supporting the role of autophagic flux inhibition in driving cell death. Conclusions: Taken together, these findings reveal that DP induces apoptosis in liver cancer cells by driving autophagosome accumulation, oxidative stress, and mitochondrial damage. Our work suggests that DP holds potential as an anthocyanin-based therapy for liver cancer. Citation Format: Anyssa Rodriguez, Samantha Tamayo, Aarya Tripathi, Sumeet Chauhan, Subash Chauhan, Nirakar Sahoo. Anthocyanin-induced autophagosome accumulation and mitochondrial dysfunction drive apoptosis in liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2828.
Abstract 1830: A chemoradiation platform for evaluating multimodal therapy effects on tumor viability and invasion ex vivo
Authors: Luda Lin, Krishna K. Bommakanti, Bowen Wang, Yazeed Alhiyari, Christian Wooten, Andreanne Sannajust, Lauran K. Evans, Peyton Tebon, Maie A. St. John, Alice Soragni
Journal: Cancer Research (2025)

Treatment of advanced head and neck squamous cell carcinoma (HNSCC) involves radiotherapy combined with chemotherapy, targeted therapy or immunotherapy. We have developed a high-throughput organoid-based drug screening platform to assess the combined effects of radiotherapy and chemotherapy or targeted therapies on HNSCC viability and invasion. To validate the platform, we used HNSCC cell lines establishing bioprinted 3D models in mini-ring format (Phan et al, 2019; Tebon et al, 2023; Al Shihabi et al 2024; Nguyen et al, 2024). Cells are exposed to X-ray radiation in combination with various small molecules and biologics. We quantified viability via ATP-release assays and extracellular matrix (ECM) invasion using a machine-learning-based brightfield image analysis pipeline (Al Shihabi et al, 2022). Proof-of-concept experiments with HPV-negative HNSCC lines (HN30 and HN31, established from primary and metastatic disease from the same patient) and HPV-positive HNSCC cells (SCC154) revealed that treatment with cetuximab and ibrutinib enhances radiosensitivity in HN31 cells. The PI3K inhibitor copanlisib radio-sensitized both HN30 and HN31, while alpelisib sensitized SCC154 cells. Additionally, copanlisib, afatinib, and ibrutinib were shown to limit ECM invasion of HN31, while the AKT inhibitor ipatasertib and the mTOR-targeting rapamycin promote invasion of HN30 cells, as observed in previous studies (Brolih et al., 2018). Our pilot experiments using bioprinted patient-derived HNSCC organoids confirmed the feasibility of performing sensitivity screening by integrating bioprinting, conventional viability assays, and advanced image analysis techniques. Our goal is to establish a personalized therapeutic pipeline for patients with advanced HNSCC, maximizing responses to radiotherapy and targeted agents to improve outcomes, and avoiding modulators that may promote tumor invasion. Citation Format: Luda Lin, Krishna K. Bommakanti, Bowen Wang, Yazeed Alhiyari, Christian Wooten, Andreanne Sannajust, Lauran K. Evans, Peyton Tebon, Maie A. St. John, Alice Soragni. A chemoradiation platform for evaluating multimodal therapy effects on tumor viability and invasion ex vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1830.
Abstract 3187: Assessing large-scale CAR-T cell cytotoxicity ex vivo using 2-D and 3-D multimodal imaging techniques for industrial standards
Authors: Catherine McManus, John Foulke, Meghan Sikes, Luping Chen, Hyeyoun Chang, Fang Tian, Zhizhan Gu
Journal: Cancer Research (2025)

Abstract CAR-T cell therapy is a revolutionary and highly effective treatment for hematologic malignancies, with rapid advancements particularly in applications to solid tumors. The development and refinement of this innovative therapy rely on efficient ex vivo assays to evaluate CAR-T cell cytotoxicity. Furthermore, advancement in the treatment of solid tumors using CAR-T cell therapy requires the development of ex vivo assays specifically using solid tumor models. Here, we report the development of luciferase reporter cancer cell lines that endogenously express high levels of key CAR-T target antigens such as CD19, CD20, BCMA, or HER2. Using targeted and mock-engineered CAR-T cells, we evaluated cytotoxicity against these reporter cells via a bioluminescence assay and phase contrast/fluorescence live imaging assays. Our multimodal imaging approach demonstrated significantly higher cancer cell killing by targeted CAR-T cells compared to mock CAR-T cells. To enhance our live imaging capabilities and enable assays for CAR-T cell infiltration into 3-D tumor models, we engineered GFP-Luc2 dual reporter cancer cell lines. Using 3-D confocal live imaging, we observed reduced spheroid size and decreased luciferase signal in Raji-GFP-Luc2 spheroids co-cultured with CD19 CAR-T cells versus mock CAR-T controls, indicating superior cancer cell killing when using targeted CAR-T cells. Upon embedding Raji-GFP-Luc2 spheroids in 3-D matrices to mimic a more physiologically relevant tumor microenvironment, we captured CAR-T cell infiltration into spheroids by time-lapse 3-D imaging. Our results highlight the utility of combining luciferase bioluminescence and live fluorescence imaging to assay CAR-T cell cytotoxicity and infiltration in 2-D and 3-D co-culture models. The luciferase assay provides sensitive, quantitative measurements, while live fluorescence imaging reveals the spatial and temporal dynamics of CAR-T cell-cancer cell interactions. These scalable assays hold significant potential for large-scale industrial applications in CAR-T cell therapy development. Citation Format: Catherine McManus, John Foulke, Meghan Sikes, Luping Chen, Hyeyoun Chang, Fang Tian, Zhizhan Gu. Assessing large-scale CAR-T cell cytotoxicity ex vivo using 2-D and 3-D multimodal imaging techniques for industrial standards [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3187.
Abstract 2822: AdipoRon suppresses breast cancer growth through autophagy-mediated ferroptosis
Authors: Yong-Han Su, Yi-Zhen Wu, Hsin-Yi Yang, Tzu-Yi Chia, Jou-Fang Hsu, Ching-Ying Kuo
Journal: Cancer Research (2025)

Abstract Excess adipose tissue and the release of large amounts of adipokines are recognized as contributing factors in the development of various cancer types. Adiponectin, distinct from other adipokines, is negatively correlated with cancer progression. Low serum levels of adiponectin have been correlated with dysregulated cellular metabolism, including lipid and glucose metabolism, as well as increased cancer cell aggressiveness. Additionally, elevated adiponectin has been characterized as an anti-tumor factor with potential as a therapeutic target. However, due to its large size and protein instability, the development of adiponectin as a drug has been challenging. Recently, an oral adiponectin receptor agonist, AdipoRon, has been identified and is currently under investigation as a potential cancer treatment. Given that breast cancer is known to be highly influenced by surrounding adipose tissue, we utilized the breast cancer cell models to further evaluate the effects of AdipoRon on cancer progression. Cell viability of various breast cancer cell lines across subtypes was reduced by AdipoRon supplementation, and autophagy was induced in a dose-dependent manner, with significant LC3 lipidation and autophagosome formation. In addition, AdipoRon led to the accumulation of free radicals in mitochondria, accompanied by morphological changes and functional disruption, which in turn caused mitophagy. Lipid metabolism of cancer cells was also impaired by AdipoRon, with a decline in fatty acid storage capacity. The increased free fatty acids were further oxidized, resulting in lipid peroxide accumulation, a hallmark of ferroptosis. Other characteristics of ferroptosis, including ferritinophagy, iron accumulation and a decrease in glutathione peroxidase 4 level, were also observed in AdipoRon-treated cells. Moreover, AdipoRon-induced cell death could be rescued by a ferroptosis inhibitor, ferrostatin, suggesting that ferroptosis was induced by AdipoRon in breast cancer cells. Mechanistically, we identified BECN1, the key regulator of autophagy, as a critical factor in AdipoRon-associated ferroptosis. Knockdown of BECN1 significantly rescued the ferroptotic cell death and related characteristics in breast cancer cells. Collectively, our data demonstrate that AdipoRon induced cell death in breast cancer cells by disrupting cellular metabolic capacity and triggering ferroptosis, a mechanism that has not been previously reported. These findings suggested the therapeutic potential of AdipoRon in inhibiting breast cancer progression. Citation Format: Yong-Han Su, Yi-Zhen Wu, Hsin-Yi Yang, Tzu-Yi Chia, Jou-Fang Hsu, Ching-Ying Kuo. AdipoRon suppresses breast cancer growth through autophagy-mediated ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2822.
Abstract 2157: Rational combination of chemotherapeutic agents with immune checkpoint inhibitors in orthotopic metastatic breast cancer models
Authors: Balaji Ramachandran, Satheeshkumar Rajendiran, Rajendran Venkidusamy, Kowshik Karmakar, Raghu Patil, Krishnappa Haladasappa
Journal: Cancer Research (2025)

Abstract Breast cancer is broadly diagnosed clinically and deadly among women. Due to heterogeneous nature of cancer and resistance, standalone treatments often fail. Consequently, combination therapy is essential as it targets multiple pathways and enhances efficacy and reduce resistance. Clinically relevant orthotopic mammary fat pads (MFP) implanted models are used for evaluating combination therapies. In the present study, we have evaluated efficacy of anti-PD1, anti-CTLA-4 antibody and Doxorubicin (DOX) as standalone and combination regimen in orthotopic breast cancer models [4T1, EMT6]. 0.5x10^6 cells were implanted orthotopically into fourth mammary fat pad. Mice were randomized based on tumor volume (∼100mm3) and treatment was initiated with anti-PD1 and anti-CTLA-4 at 10mg/kg, i.p; Q4D x 4 doses and DOX 4mg/kg, i.v; Q4Dx 4 doses as standalone or in combination. Tumor volume, changes in body weight, clinical signs, mortality, distant organ metastasis were monitored upto 4 weeks. At the end, lungs were harvested weighed, perfused with Indian ink, and fixed in 10% neutral buffered formalin for histopathology evaluation. In 4T1 tumor model, treatment with standalone anti-PD1, anti-CTLA-4, and DOX resulted in non-significant tumor growth inhibition (TGI). Whereas combination of anti-PD1 and anti-CTLA-4 with Doxorubicin demonstrated moderate TGI and marginally reduced distant organ metastasis compared to the standalone regimen. In EMT6 tumor model, standalone IO agents anti-PD1, anti-CTLA-4, and Doxorubicin treatment exhibited moderate TGI. However, combination of anti-PD1 and anti-CTLA-4 with DOX achieved synergistic significant tumor growth inhibition which was evident from absence of distant organ metastasis and resulted in prolonged survival. Overall, outcome of this study suggests combination therapy with conventional chemoagents, and immune checkpoint blockade can prevent progression to metastatic disease and may limit to overcome resistance. Such combination regimen represents a multimodal translational approach to enhance chemotherapeutic efficacy for the treatment of metastatic breast cancer. Citation Format: Balaji Ramachandran, Satheeshkumar Rajendiran, Rajendran Venkidusamy, Kowshik Karmakar, Raghu Patil, Krishnappa Haladasappa. Rational combination of chemotherapeutic agents with immune checkpoint inhibitors in orthotopic metastatic breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2157.
Abstract 2951: Development of TNFR2, TNFR1 and LTBR humanized mouse model for evaluating anti-human LTBR antibodies
Authors: Qiurong Wang, Chong Li, Zhixia Li, Zan Zhang, Jiansu Zhang
Journal: Cancer Research (2025)

The Lymphotoxin B receptor (LTBR) is primarily expressed on epithelial, stromal, and myeloid cells. LTBR signaling has diverse roles, including regulation of lymphoid organ development, induction of tertiary lymphoid structures (TLS), and promotion of liver regeneration. Recently, the therapeutic strategy of activating LTBR to induce and mature TLS has gained momentum, with LTBR-targeting antibodies now advancing into clinical trials. However, traditional preclinical models generally lack expression of human LTBR, which limits the progress of anti-human LTBR antibody development. To address this, Biocytogen has developed a humanized mouse model expressing TNFR1, TNFR2, and LTBR through Biocytogen proprietary gene editing technology, known as B-hTNFR2/hTNFR1/hLTBR mice. In these mice, humanized TNFR1, TNFR2, and LTBR expression is detected in granulocytes, regulatory T cells, and macrophages, respectively. Testing of anti-human LTBR antibodies in this model has shown effective tumor growth control, underscoring the B-hTNFR2/hTNFR1/hLTBR mouse as a valuable preclinical platform for in vivo evaluation of anti-human LTBR antibodies. Citation Format: Qiurong Wang, Chong Li, Zhixia Li, Zan Zhang, Jiansu Zhang. Development of TNFR2, TNFR1 and LTBR humanized mouse model for evaluating anti-human LTBR antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2951.