bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 1 from Modeling Drug Responses and Evolutionary Dynamics Using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple-Negative Breast Cancer
Authors: Shea Abigail , Eyal-Lubling Yaniv , Guerrero-Romero Daniel , Manzano Garcia Raquel , Greenwood Wendy , O’Reilly Martin , Georgopoulou Dimitra , Callari Maurizio , Lerda Giulia , Wix Sophia , Giovannetti Agnese , Masina Riccardo , Esmaeilishirazifard Elham , Cope Wei , Martin Alistair G. , Nagano Ai , Young Lisa , Kupczak Steven , Cheng Yi , Bardwell Helen , Provenzano Elena , Kane Justine , Lay Jonny , Grybowicz Louise , McAdam Karen , Caldas Carlos , Abraham Jean , Rueda Oscar M. , Bruna Alejandra
Published: February 2025

A preclinical platform of TNBC PDTXs. A, Clinical treatment and responses of the patient cohort from which the PDTX models used in this study were derived. B, Experimental framework of the coclinical trial. C, Top, correlation plots comparing GSEA enrichment scores (Hallmark and C6 gene sets) for models 1006, 1040, 1022, and 1141. Bottom, correlation plots comparing mutation VAFs for model 1006. Correlation was calculated between passages, sister mice, and multiple regions of the same tumor using Spearman correlation.
Key Resources Table from Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer
Authors: Haanen Terrance J. , Boock Sophie , Callahan Catherine G. , Peris Irene , Zawacki Kaitlin P. , Raines Brynne , Nino Charles A. , Tran Brian , Harold Alexis , Hodges Onishi Gabrielle , Hinderman Matthew , Dowdican Amanda , Huang Wei , Taylor Derek J. , Taylor Sarah E. , Jackson Mark W. , DiFeo Analisa , O’Connor Caitlin M. , Narla Goutham
Published: February 2025

table of key resources and reagents used in this manuscript.
IDEXX Cell Line Verification from Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer
Authors: Haanen Terrance J. , Boock Sophie , Callahan Catherine G. , Peris Irene , Zawacki Kaitlin P. , Raines Brynne , Nino Charles A. , Tran Brian , Harold Alexis , Hodges Onishi Gabrielle , Hinderman Matthew , Dowdican Amanda , Huang Wei , Taylor Derek J. , Taylor Sarah E. , Jackson Mark W. , DiFeo Analisa , O’Connor Caitlin M. , Narla Goutham
Published: February 2025

Verification of cell lines employed in this manuscript.
Table S1-S5 from The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: February 2025

Table S1-S5
EGFP OE Vector Map from Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer
Authors: Haanen Terrance J. , Boock Sophie , Callahan Catherine G. , Peris Irene , Zawacki Kaitlin P. , Raines Brynne , Nino Charles A. , Tran Brian , Harold Alexis , Hodges Onishi Gabrielle , Hinderman Matthew , Dowdican Amanda , Huang Wei , Taylor Derek J. , Taylor Sarah E. , Jackson Mark W. , DiFeo Analisa , O’Connor Caitlin M. , Narla Goutham
Published: February 2025

Vector map for the EGFP overexpression (OE) plasmid
Figure S6 from The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: February 2025

Supplementary Fig. 6. In vitro and in vivo characterization of designed circRNA.
Supplementary Figure 5 from Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling
Authors: Xu Ziyan , Kuhlmann-Hogan Alexandra , Xu Shihao , Tseng Hubert , Chen Dan , Tan Shirong , Sun Ming , Tripple Victoria , Bosenberg Marcus , Miller-Jensen Kathryn , Kaech Susan M.
Published: February 2025

Supplementary Figure 5
Figure S5 from The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: February 2025

5. cEMSY promotes ICD-driven anti-tumor immune surveillance.
Figure S3 from The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: February 2025

Supplementary Fig. 3. cEMSY induces ICD in vitro.
Supplementary Figure 2 from Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling
Authors: Xu Ziyan , Kuhlmann-Hogan Alexandra , Xu Shihao , Tseng Hubert , Chen Dan , Tan Shirong , Sun Ming , Tripple Victoria , Bosenberg Marcus , Miller-Jensen Kathryn , Kaech Susan M.
Published: February 2025

Supplementary Figure 2
Supplementary Table S1 from PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression
Authors: Zhai Fengxian , Pan Guozheng , Xue Lei , Cheng Can , Wang Jiabei , Liu Yao , Liu Lianxin
Published: February 2025

Supplementary Table S1
Supplementary Figure S8 from PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression
Authors: Zhai Fengxian , Pan Guozheng , Xue Lei , Cheng Can , Wang Jiabei , Liu Yao , Liu Lianxin
Published: February 2025

Supplementary Figure S8
Fig. S6 from Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui
Published: February 2025

Fig. S6 and its figure legend
Fig. S3 from Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui
Published: February 2025

Fig. S3 and its figure legend
Supplementary Figure S3 from PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression
Authors: Zhai Fengxian , Pan Guozheng , Xue Lei , Cheng Can , Wang Jiabei , Liu Yao , Liu Lianxin
Published: February 2025

Supplementary Figure S3
Fig. S2 from Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui
Published: February 2025

Fig. S2 and its figure legend
Fig. S1 from Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui
Published: February 2025

Fig. S1 and its figure legend
Supplementary Figure S1 from PRDM16 Induces Methylation of FLT3 to Promote FLT3-ITD Signaling and Leukemia Progression
Authors: Zhai Fengxian , Pan Guozheng , Xue Lei , Cheng Can , Wang Jiabei , Liu Yao , Liu Lianxin
Published: February 2025

Supplementary Figure S1
Table S7 from Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition
Authors: Madorsky Rowdo Florencia P. , Martini Rachel , Ackermann Sarah E. , Tang Colin P. , Tranquille Marvel , Irizarry Adriana , Us Ilkay , Alawa Omar , Moyer Jenna E. , Sigouros Michael , Nguyen John , Al Assaad Majd , Cheng Esther , Ginter Paula S. , Manohar Jyothi , Stonaker Brian , Boateng Richard , Oppong Joseph K. , Adjei Ernest K. , Awuah Baffour , Kyei Ishmael , Aitpillah Francis S. , Adinku Michael O. , Ankomah Kwasi , Osei-Bonsu Ernest B. , Gyan Kofi K. , Hoda Syed , Newman Lisa , Mosquera Juan Miguel , Sboner Andrea , Elemento Olivier , Dow Lukas E. , Davis Melissa B. , Martin M. Laura
Published: February 2025

IC50 values (µM) obtained for tested inhibitors in breast PDTO lines.
Supplementary Figures and legends from Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer
Authors: Zeng Wenfeng , Zhang Ruihua , Huang Penghan , Chen Minxia , Chen Houying , Zeng Xin , Liu Jiang , Zhang Jiahui , Huang Di , Lao Liyan
Published: February 2025

Supplementary Figures and legends
Supplementary file from Fungal Influences on Cancer Initiation, Progression, and Response to Treatment
Authors: Bilal Hazrat , Khan Muhammad Nadeen , Khan Sabir , Shafiq Muhammad , Fang Wenjie , Zeng Yuebin , Guo Yangzhong , Li Xiaohui , Zhao Bing , Lv Qiao-Li , Xu Bin
Published: February 2025

Table S1: Extra-tumoral fungi in association with various cancer types. Figure S1: Interactions of Candida species with the immune system and their roles in cancer development (a): C. albicans triggers Th17/IL-17 responses, recruiting M2-like TAMs and promoting oral cancer. (b): Candida species translocate to the liver, inducing Th17/Th1 responses, leading to inflammation and liver cancer. (c): Candida spp upregulates MDSCs in the gut, driving immune evasion in CRC. C. albicans interacts with Dectin-3 on macrophages, inducing IL-22 production and contributing to CRC. C. tropicalis interacts with CARD9-expressing macrophages, which recruit MDSCs, influencing CRC. Abbreviations: SCC, squamous cell carcinoma; IL, interleukin; CCL2, C C motif chemokine ligand 2; CD163, Cluster of differentiation 163; AGR-1, arginase 1; GAL9, galentin 9; PD-L1, Programmed death-ligand 1; CD4, Cluster of differentiation 4; MDSC, myeloid-derived suppressor cells; PD1, programmed cell death protein 1; Th, T helper; CLRs, C type lectins; ILC2, innate lymphocyte 2; GM-CSF, granulocyte-macrophage colony-stimulating factor; CTL, Cytotoxic T-lymphocyte. Figure S2: Fungal interactions with the immune system contribute to cancer development in various organs (a): Alternaria species translocate to the pancreas, driving immune suppression and pancreatic cancer. (b): Malassezia species translocate to the pancreas, driving pancreatic cancer development through C3a/C3aR signaling. (c): Aspergillus sydowii activates CARD9 macrophages and recruits MDSCs, driving immune suppression and lung cancer. (d): Highly autoreactive T cells in the esophagus lead to Cladosporium infection and activate EGFR signaling, contributing to esophageal cancer. Abbreviations: Th, T helper; IL, interleukin; CD, Cluster of differentiation; MDSC, myeloid-derived suppressor cells; PD1, programmed cell death protein 1; C3aR, C3a receptor; ILC2, innate lymphocyte 2; EGFR, Epidermal growth factor receptor. Table S2: Overview of clinical strategies targeting specific fungi for the treatment and prevention of cancer.
Table S4 from Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition
Authors: Madorsky Rowdo Florencia P. , Martini Rachel , Ackermann Sarah E. , Tang Colin P. , Tranquille Marvel , Irizarry Adriana , Us Ilkay , Alawa Omar , Moyer Jenna E. , Sigouros Michael , Nguyen John , Al Assaad Majd , Cheng Esther , Ginter Paula S. , Manohar Jyothi , Stonaker Brian , Boateng Richard , Oppong Joseph K. , Adjei Ernest K. , Awuah Baffour , Kyei Ishmael , Aitpillah Francis S. , Adinku Michael O. , Ankomah Kwasi , Osei-Bonsu Ernest B. , Gyan Kofi K. , Hoda Syed , Newman Lisa , Mosquera Juan Miguel , Sboner Andrea , Elemento Olivier , Dow Lukas E. , Davis Melissa B. , Martin M. Laura
Published: February 2025

Patient clinical information
Table S1 from Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition
Authors: Madorsky Rowdo Florencia P. , Martini Rachel , Ackermann Sarah E. , Tang Colin P. , Tranquille Marvel , Irizarry Adriana , Us Ilkay , Alawa Omar , Moyer Jenna E. , Sigouros Michael , Nguyen John , Al Assaad Majd , Cheng Esther , Ginter Paula S. , Manohar Jyothi , Stonaker Brian , Boateng Richard , Oppong Joseph K. , Adjei Ernest K. , Awuah Baffour , Kyei Ishmael , Aitpillah Francis S. , Adinku Michael O. , Ankomah Kwasi , Osei-Bonsu Ernest B. , Gyan Kofi K. , Hoda Syed , Newman Lisa , Mosquera Juan Miguel , Sboner Andrea , Elemento Olivier , Dow Lukas E. , Davis Melissa B. , Martin M. Laura
Published: February 2025

PDTO breast media composition.
Data from Multiomics Analysis Reveals Molecular Changes during Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers
Authors: Chen Yun-Ching , Hsu Chia-Lang , Wang Hui-Min , Wu Shang-Gin , Chang Yih-Leong , Chen Jin-Shing , Wu Yu-Ching , Lin Yen-Ting , Yang Ching-Yao , Lin Mong-Wei , Lee Jang-Ming , Kuo Shuenn-Wen , Chen Ke-Cheng , Hsu Hsao-Hsun , Huang Pei-Ming , Huang Yen-Lin , Yu Chong-Jen , Pirooznia Mehdi , Huang Bevan E. , Yang Rob , Shih Jin-Yuan , Yang Pan-Chyr
Published: February 2025

Abstract
Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma, the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in nonsmokers. In this study, we performed whole-exome sequencing and RNA sequencing of samples from 94 East Asian patients with precancerous lesions [25 with atypical adenomatous hyperplasia (AAH); 69 with adenocarcinoma in situ (AIS)] and 73 patients with early invasive lesions [minimally invasive adenocarcinoma (MIA)]. Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of lung adenocarcinoma. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception.

Significance: Integrative analysis of multiomics data revealed coordination between immune and nonimmune cells during early progression of precancerous lesions to lung adenocarcinomas and shed light on the molecular characteristics of clinically defined subtypes.
Data from The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: February 2025

Abstract
Immunogenic cell death (ICD) induces an active immune response. Activating ICD represents a potential approach to boost the antitumor activity of immunotherapy, highlighting the need to identify effective and safe ICD inducers. In this study, we identified a conserved, ICD-related circular RNA cEMSY by systematically screening ICD models induced by multiple cell stressors in lung adenocarcinoma. cEMSY triggered ICD in lung adenocarcinoma cells both in vitro and in vivo, leading to the release of damage-associated molecular patterns and promoting T-cell cross-priming by dendritic cells. Notably, the intratumoral delivery of lipid nanoparticle–encapsulated cEMSY induced a potent antitumor immune response in an immunosuppressed tumor model, which synergized with PD-1 blockade to facilitate long-term antitumor immunity with no apparent toxicities. Mechanistically, cEMSY mediated mitochondrial aggregation of the RNA-binding protein TDP-43 that enabled leakage of mitochondrial DNA to stimulate the cGAS–STING pathway, activating the antiviral immune response. Clinically, elevated expression of cEMSY correlated with enhanced infiltration of dendritic cells and CD8+ T cells and favorable immunotherapy response in lung adenocarcinoma. Together, these findings support the dual potential of cEMSY as a target and biomarker for improving immune checkpoint inhibitor responses in lung adenocarcinoma.

Significance: cEMSY is a safe and effective immunogenic cell death inducer that synergizes with PD-1 blockade in lung adenocarcinoma, providing a potential strategy to enhance the efficacy of tumor immunotherapy.
Data from Loss of CDKN2A Enhances the Efficacy of Immunotherapy in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Wang Simeng , Lai Jia-Cheng , Li Yu , Tang Chengfang , Lu Jiajia , Han Min , Ye Xianjiang , Jia Lina , Cui Wei , Yang Jingyu , Wu Chunfu , Wang Lihui
Published: February 2025

Abstract
Mutant EGFR is a common driver of non–small cell lung cancer (NSCLC). Although mutant EGFR has been reported to limit the efficacy of immunotherapy, a subset of patients with EGFR-mutant NSCLC benefit from treatment with immune checkpoint inhibitors. A better understanding of how co-occurring genomic alterations in oncogenic driver genes impact immunotherapy efficacy may provide a more complete understanding of cancer heterogeneity and identify biomarkers of response. Here, we investigated the effects of frequent EGFR co-mutations in EGFR-mutant lung cancer models and identified loss-of-function mutation of CDKN2A as a potential sensitizer to anti–PD-1 treatment in vitro and in vivo. Mechanistically, CDKN2A loss impacted the composition of the tumor immune microenvironment by promoting the expression of PD-L2 through reduced ubiquitination of c-MYC, and mutant EGFR cooperating to upregulate c-MYC and PD-L2 by activating the MAPK pathway. Blocking PD-L2 induced antitumor immune responses mediated by CD8+ T cells in EGFR/CDKN2A co-mutated lung cancer. Importantly, a small-molecule PD-L2 inhibitor, zinc undecylenate, remodeled the tumor immune microenvironment of EGFR/CDKN2A co-mutant tumors and enhanced the antitumor efficacy of EGFR tyrosine kinase inhibitors. Collectively, these results identify EGFR/CDKN2A co-mutation as a distinct subtype of NSCLC that shows superior sensitivity to immune checkpoint blockade and reveals a potential combined therapeutic strategy for treating this NSCLC subtype.

Significance: Upregulation of c-MYC driven by co-mutation of CDKN2A and EGFR increases PD-L2 to abrogate CD8+ T-cell activity in lung cancer, which confers sensitivity to PD-L2 blockade in combination with tyrosine kinase inhibitors.
In Search of Representative Translational Cancer Model Systems
Authors: Trembath Hannah E. , Spanheimer Philip M.
Published: February 2025

Racial disparities in cancer outcomes are well documented across tumor types. For patients with breast cancer, Black women are more likely to present with more aggressive molecular features and more likely to die from disease, even after accounting for those features. Recent efforts have been aimed at developing translational model systems for precision medicine strategies, and a major focus has been on patient-derived organoids. Organoids allow for robust in vitro experimental platforms, including drug and CRISPR screens while maintaining more complex cancer and tumor microenvironment subpopulations than cell lines. For results that are broadly translationally relevant, it is important that cancer models are derived from the spectrum of human disease and humans with disease. In this issue of Cancer Research, Madorsky Rowdo and colleagues derive breast cancer organoids from patients with African ancestry and use CRISPR-Cas9 screens to identify novel therapeutic vulnerabilities. These findings demonstrate the promise of representative cancer model systems to facilitate discoveries that are most likely to translate to improved therapy for all patients.

See related article by Madorsky Rowdo et al., p. 551
Abstract A019: CRISPR-based investigation of CHIP mutations reveals their role in CAR-T therapy-related inflammatory toxicities
Authors: Wang Xiuli , Goldsmith Scott R. , Rhee June-Wha , Forman Stephen J. , Zhang Chunyan , Armenian Saro
Published: February 2025

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by somatic mutations (e.g. DNMT3A, TET2, and ASXL1I) in hematopoietic stem cells, and linked to age-related clonal expansions and inflammatory states. We previously showed that patients with CHIP receiving CAR-T cell therapy have a four-fold risk of developing clinically significant cytokine release syndrome (CRS) compared to those without CHIP (Transplant Cell Ther 2024). This prompted us to investigate the mechanisms through which CHIP mutations could contribute to CAR-T-related toxicities. Methods: We employed CRISPR-based gene editing to target CHIP-associated genes—DNMT3A, TET2, and ASXL1—in M1-like macrophages, which were differentiated from human monocytes in the presence of 20 ng/mL of GM-CSF. Gene perturbation was achieved with cell-penetrating phosphorothioated single-stranded DNA oligonucleotides to deliver the CRISPR-Cas9 and gRNA complex (PS-Cas9/gRNA). Editing was performed using multiple gRNAs for each gene: DNMT3A (2 gRNAs), TET2 (3 gRNAs), and ASXL1 (2 gRNAs), and decreased protein expression was confirmed post-editing. We co-cultured CS1 CAR-T cells targeting multiple myeloma (MM), MM.1S cells, and edited autologous macrophages at a 1:1:0.1 ratio for 24 hours to assess the inflammatory response. Cytokine secretion was quantified using the LEGENDplex™ Human Inflammation Panel 1 (13-plex). Results: Compared to non-edited macrophages, DNMT3A-, TET2-, and ASXL1-edited macrophages consistently secreted significantly higher levels of IL-6 (642, 920, 1338 pg/ml vs. 325 pg/ml respectively, P<0.05-0.001), MCP-1(90, 122, 151 pg/ml vs. 55 pg/ml, respectively, P<0.01-0.001), TNFα (2015, 1722, 1874 pg/ml vs. 1043 pg/ml, respectively P:ns - < 0.001), IL-1β (75, 99, 146 pg/ml vs. 38 pg/ml, respectively, P<0.05-0.001), and IL-8 (21, 19, 22 ng/ml vs. 15 ng/ml, respectively, P:ns- <0.001). Conclusions: These findings suggest CHIP mutations in human macrophages may exacerbate the inflammatory response in CAR-T therapy, highlighting a potential biomarker for stratifying patients at higher risk for toxicities such as CRS and guiding more personalized prophylactic interventions.

Citation Format: Xiuli Wang, Scott R. Goldsmith, June-Wha Rhee, Stephen J. Forman, Chunyan Zhang, Saro Armenian. CRISPR-based investigation of CHIP mutations reveals their role in CAR-T therapy-related inflammatory toxicities [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr A019.
Abstract B007: Epigenetic reactivation of transposable elements as prognostic markers for PD1/PDL1 immunotherapy in cancer
Authors: Wu Yixin , Wang Ting , Liang Yonghao
Published: February 2025

Transposable elements (TEs), once considered as "junk" DNA, are now recognized for their epigenetic and regulatory influence, especially in cancer. Cryptic regulatory elements within TEs can be epigenetically reactivated in cancer, contributing to oncogenesis and altering gene expression patterns. This reactivation results in TE-derived transcripts, which have the potential to be translated and form neoantigens that can be presented by the human leukocyte antigens (HLA) complex and recognized by T cells, ultimately impacting the tumor immune response. In this study, we analyzed RNA-seq data from melanoma patients undergoing PD1/PDL1 immunotherapy. By identifying tumor specific TE-derived transcripts and utilizing in silico translation, we detected TE-derived neoantigens in patients with differing responses to immunotherapy. Our findings indicate that the number of TE-derived neoantigens is correlated with patients' response to immunotherapy, with a higher number of neoantigens observed in patients who responded to treatment compared to those who did not. These results imply that TE-derived neoantigens may serve as potential biomarkers for predicting the prognosis of PD1/PDL1 immunotherapy treatment. Incorporating TE-derived neoantigen profiles into clinical decision-making could enhance patient selection for immunotherapy, thereby improving treatment outcomes.

Citation Format: Yixin Wu, Ting Wang, Yonghao Liang. Epigenetic reactivation of transposable elements as prognostic markers for PD1/PDL1 immunotherapy in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B007.
Abstract B013: Gene-body DNA methylation of ONECUT2 predicts its expression status and prostate cancer aggressiveness in clinic specimens
Authors: Liang Gangning , Liang Gangning
Published: February 2025

ONECUT2 is a lineage plasticity driver and therapeutic target in aggressive prostate cancer (PCa). The goal of this study was to determine the role of ONECUT2 gene-body DNA methylation in regulating its expression and to evaluate its potential as a biomarker and therapeutic target for aggressive PCa. We observed a robust positive correlation between ONECUT2 expression levels and gene-body DNA methylation. This role was confirmed in prostate cancer cells through treatment with a DNA methylation inhibitor (DNMTi). Targeted bisulfite sequencing was performed to measure ONECUT2 gene-body DNA methylation in 208 needle biopsies from PCa patients, revealing a correlation between ONECUT2 gene-body hypermethylation and aggressive features. Thus, measuring ONECUT2 gene-body DNA methylation in clinical specimens can provide a predictive assessment of disease progression before surgery. Our results also suggest that downregulating ONECUT2 expression using DNMTi may be a viable therapeutic strategy for treating aggressive PCa.

Citation Format: Gangning Liang, Gangning Liang. Gene-body DNA methylation of ONECUT2 predicts its expression status and prostate cancer aggressiveness in clinic specimens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B013.
Abstract B027: Modeling age-related DNA methylation changes with intestinal organoids
Authors: Vaidya Himani , Calendo Gennaro , Pompetti Anthomy , Balch Curt , Keith Kelsey , Mazdo Jozef , Jelinek Jaroslav , Issa Jean-Pierre
Published: February 2025

Intestinal organoids, three-dimensional cultures from intestinal stem cells, are a potential model for studying aging. DNA methylation can serve as biological clock of aging, and we hypothesized that organoid DNA methylation could be a valuable tool for aging research. We compared DNA methylation in organoids to that seen in primary aging intestinal epithelium. Genome wide, we found very substantial DNA methylation changes during organoid establishment and culture, with 27% of total CpG sites undergoing loss of methylation (hypomethylation), and 11% gaining methylation (hypermethylation). The observed hypermethylation primarily affected CpG islands and corresponded to CpG sites susceptible to age-related methylation in-vivo (p < 0.001 compared to unchanged sites). Early-passage (P0 and P2) organoids derived from 4- and 24-month-old mice, preserved aging-specific methylation patterns, with a correlation coefficient of 0.48 (p < 0.001) between methylation differences in-vivo and in-vitro. Age-related hypermethylation continued to change with passage, and linear modeling indicated that organoids age at an average rate of 0.46 months per week in culture. By contrast, hypomethylation occurred predominantly in non-aging-associated genomic regions such as non-promoter, non-CpG island regions (including transposable elements), and correlated neither with differentiation nor aging in-vivo. Thus, methylation changes in organoids reflect at least two different biological processes – aging, as measured by CpG island hypermethylation, and an unexplained stochastic hypomethylation defect. Treatment with the DNA methylation inhibitor decitabine lowered the methylation age of organoids from 22 months to 10 months, showing the potential of organoids to model extrinsic effects on age-related DNA hypermethylation.

Citation Format: Himani Vaidya, Gennaro Calendo, Anthomy Pompetti, Curt Balch, Kelsey Keith, Jozef Mazdo, Jaroslav Jelinek, Jean-Pierre Issa. Modeling age-related DNA methylation changes with intestinal organoids [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr B027.
Abstract IA011: Heterochromatin deregulation during hematopoietic stem progenitor cell (HSPC) aging
Authors: Hong Tingting , Guo Lei , Guzman Anna , You James , Goodell Margaret , Zhou Yubin , Huang Yun
Published: February 2025

Aging is one of the major negative factors affecting normal hematopoiesis. Aged hematopoietic stem and progenitor cells (HSPCs) exhibit reduced self-renewal and increased myeloid bias during lineage specification, thereby sabotaging the immune system and increasing the risk of malignant transformation. Epigenetic dysregulation is a hallmark feature of aging and significantly contributes to age-related dysfunction across multiple biological systems. DNA methylation drift is commonly observed during aging, especially within late-replicated heterochromatin. DNA methylation and demethylation are maintained by DNMT and TET enzymes. Mutations in DNMT3A and TET2 are frequently observed in age-related clonal hematopoiesis (CH) and hematological malignancies. The impact of DNMT3A or TET2 loss-of-function on heterochromatin has recently gained recognition. Although heterochromatin is generally regarded as a gene-less region, it plays an important role in maintaining genome stability. Recently, we compared the impact of aging on WT and Tet2 knockout (KO) HSPCs. We observed that aging has less impact on Tet2KO HSPCs, which retain considerable clonal expansion capability during aging. However, WT HSPCs exhibited functional decline with age. At the molecular level, we identified the spatial relocation of heterochromatin from the nuclear periphery to the intranuclear region in aged WT HSPCs, but not in Tet2KO HSPCs. This relocation resulted in the upregulation of endogenous retroviruses (ERVs) and the promotion of innate immune responses in WT HSPCs, contributing to their functional decline during aging. This study adds a new dimension to understanding the functional interplay between DNA methylation and histone modifications in maintaining heterochromatin integrity and genome stability during stem cell aging.

Citation Format: Tingting Hong, Lei Guo, Anna Guzman, James You, Margaret Goodell, Yubin Zhou, Yun Huang. Heterochromatin deregulation during hematopoietic stem progenitor cell (HSPC) aging [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA011
Abstract IA014: Clinial implications of clonal hematopoiesis - and the role of Vitamin C
Authors: Grønbæk Kirsten
Published: February 2025

Dr Grønbæk will discuss the management of clonal hematopoiesis (CH) in clinical practice, focusing on how people with CH are identified. She will elaborate on the importance of identifying and following high-risk individuals/patients while sparing low risk individuals unnecessary worries. The role of DNA methylation changes in CH and low risk myeloid cancer will be discussed, including how preclinical studies have fostered the first clinical trials in CH. A special focus will be on the role of ascorbic acid (vitamin C) in CH and myeloid precursor conditions. Clinical- and correlative data from a randomized placebo controlled clinical trial: NCT03682029: A randomized, placebo-controlled, blinded, parallel-group clinical phase 2 study of oral vitamin C vs Placebo in CCUS/LR-MDS (EVITA) will be presented. The importance of enrolling these individuals/patients in clinical trials will be discussed including the optimal trials designs.

Citation Format: Kirsten Grønbæk. Clinial implications of clonal hematopoiesis - and the role of Vitamin C [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA014
Abstract PR004: Interplay between histone modifications and DNA methylation in cancer
Authors: Lu Chao
Published: February 2025

During solid tumor development, gene-poor and lamina-associated genomic regions undergo progressive loss of DNA methylation, whereas promoter CpG islands become DNA hypermethylated. We report evidence suggesting that the recruitment of DNMT3A by histone modifications contributes to this cancer-associated DNA methylome reprogramming. The genomic targeting of DNMT3A is regulated by the competition between NSD1-mediated histone H3K36 methylation and polycomb-mediated H2AK119 ubiquitination, via DNMT3A's PWWP domain and N-terminal ubiquitin-interacting region, respectively. Mutations in NSD1, DNMT3A reader domains or polycomb complexes perturb DNMT3A recruitment and can recapitulate patterns of DNA methylation observed in patient tumors. Lastly, tumors exhibiting progressive hypomethylation, such as those harboring NSD1 mutations, are paradoxically immune-cold despite the increased expression of retrotransposons. These results suggest that DNA hypomethylation and aberrant retrotransposon activation are significant bottlenecks to tumor development and may represent promising therapeutic targets.

Citation Format: Chao Lu. Interplay between histone modifications and DNA methylation in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr PR004.
God, the Feminine, and Other Struggles
Authors: Verde Danilo
Published: February 2025

This review examines three recent contributions to the Song of Songs scholarship by Nina S. Heereman, Vita Daphne Arbel, and Elaine T. James & Simeon B. Chavel, each offering fresh perspectives on this celebrated biblical poem. Heereman proposes a symbolic interpretation that integrates anthropological and theological dimensions. Focusing on the “most beautiful woman,” Arbel applies gender studies to explore the poem’s complex and fluid depictions of femininity. James and Chavel, inspired by the MeToo movement, connect the Song to contemporary debates on gender, power, and violence, with several chapters offering a reparative reading. Together, these works highlight the Song’s unique ability to inspire dialogue across multiple fields, demonstrating how both the text itself and the conceptual frameworks of its readers contribute to its rich interpretive possibilities.
dumu diĝir-ra-na: Divine Filiation in Mesopotamian Incantation Literature
Authors: Agnethler Hannelore , Baragli Beatrice
Published: February 2025

This article tackles the question of divine filiation in the ancient Near East, analysing the Sumerian phrase dumu diĝir-ra-na “the child of his/her god.” This characteristic phrase appears almost exclusively within incantation literature and designates the patient. The article proposes that this phrase implies a specific kind of relationship between the patient and his “personal god(s)” and traces the historical development of the phrase by comparing an up-to-date collection of attestations (included as an appendix) with other phrases indicating the patient in Sumerian and Akkadian sources. The article concludes that dumu diĝir-ra-na first occurs in the Old Babylonian period and is distinct from other terms for patients in that it stresses reconciliation between the patient and the personal god as necessary for the patient’s healing. Texts that include this phrase and express the concept of reconciliation employ a rhetoric that relates a specific role to each speaker.
American Abortion Culture Wars as Religious Populism: “Truth” and “Fight for Truth” as Floating Signifiers
Authors: Oh Dayei
Published: February 2025

This paper explores the American abortion culture wars through the lens of religious populism, focusing on online discourse of the Christian pro-life confederation, Personhood Alliance. Drawing on Laclaudian post-foundationalist theories, the paper conceptualizes culture wars as a populist logic of meaning-making, where the floating signifier “truth” is central to mobilizing support and constructing Us-Them boundaries. The analysis identifies two key floating meanings of “truth”: restoring divine, cultural, and scientific truth about personhood, and battling the perceived conspiracies of the liberal abortion establishment. Hybrid media ecologies provide a controlled space for the movement to disseminate narratives circumventing platform moderation. The movement’s affective Us-Them construction portrays “Us” as righteous truth-seekers and saviours of the marginalized, while “Them” is cast as a corrupt liberal elite deceiving and exploiting the marginalised. This affective dichotomy expands abortion culture wars beyond the Christian pro-life base, inviting marginalized groups to join the fight against the establishment.
A Populist, Influencer, and Religious Politician
Authors: Vuković Silvija , Krapić Nina
Published: February 2025

Celebrity populism describes a combination of populism and celebrity politics in contemporary political communication. This paper narrows the concept down, as we present what we recognize as a populist influencer politician – a populist politician who is performing in a style of an influencer. Moreover, we analyze a specific role religion plays in the construction of populist messages. The empirical part centers on Marin Miletić, a populist politician and former religion teacher from Croatia who is communicating as an influencer on social media. Qualitative content analysis of Miletić’s Instagram Stories during the Croatian parliamentary election campaign in 2024 unravels how he combines political, religious, and private personas on social media. The paper provides detailed examples of how influencer style and religion content emphasize his populist messages. At the same time, we shed light on the blurred lines between entertainment, politics, populism, and religion in contemporary political communication.
#Girlhood: Why Memetic Aesthetics of Hyperfemininity Matter for Feminist Media Studies
Authors: Wiens Brianna I. , McWebb Anna
Published: February 2025

There is a pressing need to focus attention on hyperfemininity as a valid and valued form of gender expression and feminist protest within contemporary social media. As resistance against the heteropatriarchal gender expectations that influence femininity and that produce femmephobia, we focus our analysis on the social media #girlhood meme trend that, we suggest, embraces a wide range of femme practices through the re-mixing of fem(me)ininity and femme-ness, while critiquing heteropatriarchal norms. We trace the circulation of #girlhood, including coquette aesthetics, #barbiecore, and #bimbofeminism, outlining how these playful expressions of femininity contribute to subverting expectations of “successful” femme bodies. We argue that if gender norms are scripts that prescribe and describe how we must act, then widening the range of acceptable feminine behaviour through hyperfemininity, as manifest in #girlhood memes, is crucial for changing how we discipline femme bodies and how we analyze femininity within media studies.
From Helplessness to Purpose: Beginning a Journey in Surgery
Authors: Farah Amir
Published: February 2025

This piece explores a personal path to becoming a surgeon, driven by a moment of helplessness at a beloved family member’s bedside. Unable to alleviate their suffering, the sense of inadequacy and helplessness fueled a determination to pursue surgery, particularly trauma surgery. Through rigorous training, purpose was found in the ability to act decisively and compassionately in moments of crisis. This journey, shaped by personal loss, reflects how vulnerability can transform into a deep commitment to healing and service of those in need.
Prosodic Cues for Broad, Narrow, and Corrective Focus in Persian
Authors: Taheri-Ardali Mortaza , Roessig Simon , Pagel Lena , Mücke Doris
Published: February 2025

Previous studies have demonstrated that focus significantly alters sentential prosody in Persian. However, research on the phonetic realization of non-corrective narrow focus is scarce compared to that on broad and corrective focus. This paper presents a systematic production study investigating whether Persian speakers distinguish between three focus structures on target words that bear a pitch accent, that is, broad, narrow, and corrective focus. In a multidimensional phonetic analysis, we investigated the parameters of intensity, duration, and F0. Taking a local perspective, results show that the duration of the target word is a robust cue for focus marking in both syllables of the word, exhibiting a three-step pattern (corrective > narrow > broad). In the first syllable, intensity is a reliable cue to distinguish broad focus from the other two focus types, with higher intensities in broad focus. In the accented syllable, a different two-step pattern is observed, with narrow and corrective focus showing larger F0 spans than broad focus. Taking a global perspective that considers the parts of the utterance before and after the target word, we find a lowering of F0 and decreased intensity for narrow and corrective focus in the pre-target region. In the post-target region, we find strong evidence for differences in mean F0 and intensity with lower F0 in corrective focus than in broad and narrow focus, while the intensity is lower in narrow and corrective focus than in broad focus. Our analysis deepens our understanding of Persian prosody.
Political, Cultural, or Religious: How Do People Construe Religious Identity in Post-Conflict Societies?
Authors: Baysu Gülseli , Uluğ Özden Melis
Published: February 2025

This study investigates the understudied aspect of the multi-faceted nature of religious identity and its implications for intergroup outcomes vital to (post-)conflict settings. Three studies were conducted in Northern Ireland to address this gap using a mixed-method approach. Study 1 involved 519 Catholic and Protestant participants who provided open-ended responses regarding religious identity construals as religious, cultural, or political. Qualitative content analysis yielded 17 items related to Catholic/Protestant identity construals. Study 2 included 276 participants who rated these 17 items, and factor analyses identified a subset of 14 items representing the three identity construals. Finally, Study 3 ( N = 300) validated the newly-developed scale and examined how different combinations of religious, cultural, and political identities related to forgiveness, collective action, and allyship. The results indicate the reliable measurement of religious identity construals across the three dimensions and contribute to understanding religious identity and its implications for conflict and peace.
Reliability and Validity of Turkish Translation of the Questionnaire of Physiotherapeutic Specific Exercises of Scoliosis (QPSSE): A Brief Report
Authors: Gökalp Burcu Şenol , Karatel Kamile Merve , Yağcı Gözde , Yakut Yavuz
Published: February 2025

This study aimed to evaluated the reliability and validity of the Turkish adaptation of the Questionnaire of Physiotherapeutic Specific Exercises of Scoliosis (QPSSE). Fifty-one individuals who had been performing scoliosis-specific exercises (PSSEs) for at least two months completed the QPSSE. Validity was analyzed by correlating the QPSSE with the Scoliosis Research Society-22 (SRS-22) questionnaire and the Scoliosis Japanese Questionnaire-27 (SJ-27). The intraclass correlation coefficients ( ICC) were used to estimate test-retest reliability. The QPSSE demonstrated excellent internal consistency (Cronbach’s alpha coefficients were .90 and .93) and test-retest reliability ( ICC = .92, 95% confidence interval [.86–.95]). The QPSSE also demonstrated strong construct validity with the SRS-22 ( r = −.57) and SJ-27 ( r = −.66) total scores. The Turkish QPSSE is a valid and reliable questionnaire for evaluating the physical functioning, self-image, PSSEs, psychosocial functioning, cognitive functioning, compliance, motivation, and pain-related physiotherapeutic specific exercises of scoliosis in idiopathic scoliosis.
Jealousy in interracial and same-race relationships
Authors: Pham Vikki , Sasaki Eri , Naeimi Hanieh , Impett Emily A
Published: February 2025

Interracial relationships have been on the rise and face unique relational challenges but are underrepresented in relationship science which has relied heavily on studies of same-race White couples. Existing research has shown that individuals in interracial relationships experience greater jealousy than those in same-race relationships, but these studies were underpowered or relied on binary measures of jealousy. In a large sample of individuals in interracial ( N = 196) and same-race relationships ( N = 198) from the United States and Canada, we found that individuals in interracial relationships reported experiencing jealousy more frequently and intensely (general jealousy), had greater worries about potential romantic rivals (rival-directed cognitive jealousy), and felt more distrust and anger toward rivals (rival-directed emotional jealousy). However, there were no differences in the extent to which they derogated the rival and displayed their relationship in front of the rival (rival-directed behavioral jealousy), and the findings for general and cognitive jealousy became nonsignificant when controlling for attachment anxiety. Finally, having a stronger couple identity attenuated the negative effects of having higher general jealousy and cognitive jealousy on relationship satisfaction for individuals in interracial (but not same-race) relationships. Future research should explore the development of attachment anxiety in interracial relationships and explore strategies in addition to having a stronger couple identity that can help interracial couples navigate third-party threats more effectively.