{"title":"Ferroptotic tumor cells reprogram tumor-associated macrophage antigen presentation to enhance the efficacy of immune checkpoint blockade.","authors":"Jia-Lei Sun, Yong-Chao Chu, Fu Wang, Ding-Dang Yu, Jin-Rui Liu, Ru-Chen Xu, Hua-Hua Liu, Zhuo-Ran Qi, Xuan Shi, Xiang-Nan Yu, Yi-Kun Yao, Tao-Tao Liu, Shu-Qiang Weng, Ling Dong, Xi-Zhong Shen, Shi-Bin Hu, Tao Sun, Ji-Min Zhu","doi":"10.1016/j.xcrm.2026.102774","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102774","url":null,"abstract":"<p><p>Although evidence links ferroptosis to tumor immunity, the rationale and translational potential of ferroptosis-based therapy remain unresolved. Here, we show that inducing tumor-cell ferroptosis enhances anti-tumor immunity by potentiating major histocompatibility complex II (MHC-II)-dependent antigen presentation in tumor-infiltrating macrophages. Multi-omics analyses reveal that all-trans retinoic acid (ATRA) released from ferroptotic tumor cells directly targets CD38 through the transcriptional factor retinoic acid receptor alpha (RARα) and activates transcription factor EB (TFEB) to control MHC-II expression in macrophage by inducing autophagy. Clinically, a ferroptosis signature correlates with improved immunotherapy response. We also developed a drug-free nano-redox lever that selectively targets and disrupts glutathione metabolism in hypoxic tumor regions by accepting electrons, thereby potentiating ferroptosis-mediated immune stimulation. This creates a positive feedback loop wherein activated macrophages further promote immune-driven tumor ferroptosis, synergizing with anti-PD-1 (programmed cell death protein 1) therapy across preclinical models. Together, our study identifies an uncovered role for ferroptosis in tumor immunity and provides a clinically translatable approach to enhance immunotherapy efficacy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102774"},"PeriodicalIF":10.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Misty Shuo Zhang, Kenneth Kin-Leung Kwan, Aki Pui-Wah Tse, Gengchao Wang, Larry Lai Wei, Kejie Sun, Noreen Nog-Qin Chui, Derek Lee, Macus Hao-Ran Bao, Xiaoxuan Pang, Zhenqi Wu, Yanyan Chen, Yangyang Wang, Zifan Yang, Xue Jiang, Qidong Li, Yan Zhang, Yajie Zhong, Jacinth Wing-Sum Cheu, Yiling Chen, Weixing Li, Chun-Ming Wong, Jianing Wang, Zongwei Cai, Qi Zhang, Tingbo Liang, Irene Oi-Lin Ng, Adonia E Papathanassiu, Carmen Chak-Lui Wong
{"title":"BCAT1-dependent HIF-1α stabilization is a targetable metabolic vulnerability in hepatocellular carcinoma.","authors":"Misty Shuo Zhang, Kenneth Kin-Leung Kwan, Aki Pui-Wah Tse, Gengchao Wang, Larry Lai Wei, Kejie Sun, Noreen Nog-Qin Chui, Derek Lee, Macus Hao-Ran Bao, Xiaoxuan Pang, Zhenqi Wu, Yanyan Chen, Yangyang Wang, Zifan Yang, Xue Jiang, Qidong Li, Yan Zhang, Yajie Zhong, Jacinth Wing-Sum Cheu, Yiling Chen, Weixing Li, Chun-Ming Wong, Jianing Wang, Zongwei Cai, Qi Zhang, Tingbo Liang, Irene Oi-Lin Ng, Adonia E Papathanassiu, Carmen Chak-Lui Wong","doi":"10.1016/j.xcrm.2026.102784","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102784","url":null,"abstract":"<p><p>Hypoxia is a common characteristic of solid tumors, especially in hepatocellular carcinoma (HCC). Hypoxia-inducible factors (HIFs), particularly HIF-1α, mediate metabolic adaptation, which is crucial for survival of hypoxic cells. Branched-chain amino transferase 1 (BCAT1) catalyzes the reversible transamination reaction between branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs), involving the inter-conversion of α-ketoglutarate (α-KG) and glutamate. We investigate and delineate the mechanisms by which BCAT1 consumes α-KG and stabilizes HIF-1α, suppressing α-KG-dependent oxygen dehydrogenase, prolyl hydroxylase-domain protein (PHD), inducing HIF-1α-mediated metabolic reprogramming and promoting hypoxic survival of HCC. We evaluate the potency of a BCAT1 inhibitor, ERG245, as a single or combination treatment with tyrosine kinase inhibitor (TKI) in vivo. We further validate the over-expression and correlation of BCAT1 and HIF-1α downstream metabolic genes in HCC clinical samples. Our results indicate that BCAT1 benefits HCC growth through HIF-1α-induced metabolic reprogramming. Targeting BCAT1 will provide an effective therapeutic strategy for HCC patients.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102784"},"PeriodicalIF":10.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pradip Bajgain, Yang Feng, Mariela Puebla, Meijie Tian, Kuo-Sheng Hsu, Jaewon Lee, GuoJun Yu, Liping Yang, Steven Seaman, Mary Beth Hilton, Karen Morris, Niza Borchin, Jennifer D Tran, Riley D Metcalfe, Dan Li, Mitchell Ho, James C Cronk, Javed Khan, Anandani Nellan, Rosandra N Kaplan, Brad St Croix
{"title":"Engineering functionality-optimized fully human B7-H3 CAR T cells for enhanced solid tumor therapy.","authors":"Pradip Bajgain, Yang Feng, Mariela Puebla, Meijie Tian, Kuo-Sheng Hsu, Jaewon Lee, GuoJun Yu, Liping Yang, Steven Seaman, Mary Beth Hilton, Karen Morris, Niza Borchin, Jennifer D Tran, Riley D Metcalfe, Dan Li, Mitchell Ho, James C Cronk, Javed Khan, Anandani Nellan, Rosandra N Kaplan, Brad St Croix","doi":"10.1016/j.xcrm.2026.102782","DOIUrl":"10.1016/j.xcrm.2026.102782","url":null,"abstract":"<p><p>B7-H3 is a cell surface protein overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR) T cell therapy. The most clinically advanced B7-H3 CARs derive from murine monoclonal antibodies (mAbs) 376.96 and MGA271 and are now in phase 1/2 trials. However, non-human mAb sequences can provoke immune responses, leading to CAR T cell rejection and therapeutic failure. Although single-chain variable fragment (scFv) humanization reduces this risk, residual foreign residues within variable domains remain. To overcome this limitation, here we use in vitro phage display to generate fully human B7-H3-specific scFvs for CAR design. In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 are well tolerated and demonstrate superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induces complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102782"},"PeriodicalIF":10.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brigitte L Arduini, Timothy A Blenkinsop, Michael Naimark, Susan Borden, Carol Charniga, Melissa Campbell, Natasha Rugenstein, Richard J Davis, Nazia Alam, Glen Prusky, Amber M Frye, Francesca Mazzoni, Silvia C Finnemann, Cuiping Zhao, Patricia Lederman, Janmeet S Saini, Thomas R Kiehl, Nicole Renga, Jade A Kozak, Penny A Rocchio, Enrique Salero, Nathan C Boles, Susan K Goderie, Steven Lotz, Joan E Adamo, Sharyl Zaccaglino, Khadijah Onanuga, Michael Fiske, Alexandra Capela, Sally Temple, Jeffrey H Stern
{"title":"IND-enabling safety and efficacy of RPESC-RPE-4W, an adult RPE progenitor cell therapy for dry age-related macular degeneration.","authors":"Brigitte L Arduini, Timothy A Blenkinsop, Michael Naimark, Susan Borden, Carol Charniga, Melissa Campbell, Natasha Rugenstein, Richard J Davis, Nazia Alam, Glen Prusky, Amber M Frye, Francesca Mazzoni, Silvia C Finnemann, Cuiping Zhao, Patricia Lederman, Janmeet S Saini, Thomas R Kiehl, Nicole Renga, Jade A Kozak, Penny A Rocchio, Enrique Salero, Nathan C Boles, Susan K Goderie, Steven Lotz, Joan E Adamo, Sharyl Zaccaglino, Khadijah Onanuga, Michael Fiske, Alexandra Capela, Sally Temple, Jeffrey H Stern","doi":"10.1016/j.xcrm.2026.102779","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102779","url":null,"abstract":"<p><p>Dry age-related macular degeneration (AMD) is a prevalent blinding disorder characterized by loss of retinal pigment epithelium (RPE) cells and resulting central vision impairment. Here, we describe preclinical studies supporting an investigational new drug (IND) application for adult RPE stem cell-derived RPE (RPESC-RPE) cell replacement therapy. We establish donor-to-donor reproducibility and Good Manufacturing Practice (GMP) processes and evaluate the GMP cell product in preclinical studies conducted in accordance with Good Laboratory Practice principles. Efficacy experiments in Royal College of Surgeons rats show that subretinal implantation of the 4-week, postmitotic, progenitor-stage product (RPESC-RPE-4W) produces significant and durable vision rescue compared to vehicle control. Biodistribution and safety studies in immunocompromised Rowett Nude rats demonstrate a favorable safety profile, with no adverse effects related to the cell product. These studies underpin allowance of an ongoing phase 1/2a clinical trial.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102779"},"PeriodicalIF":10.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophie Paczesny, Sonali P Barwe, Anilkumar Gopalakrishnapillai, Nai-Kong V Cheung
{"title":"T cell-engaging bispecific antibodies for myeloid malignancies: Targets, formats, and clinical challenges.","authors":"Sophie Paczesny, Sonali P Barwe, Anilkumar Gopalakrishnapillai, Nai-Kong V Cheung","doi":"10.1016/j.xcrm.2026.102772","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102772","url":null,"abstract":"<p><p>T cell-engaging bispecific antibodies (T-BsAbs) have revolutionized immunotherapy for hematologic malignancies, showing promise in lymphoid cancers and myeloma. However, their application in myeloid malignancies like acute myeloid leukemia (AML) faces challenges due to myelotoxicity and limited target specificity. Here, we review the current landscape of T-BsAb development for myeloid diseases, detailing target antigens, antibody engineering strategies, and clinical trial outcomes. We discuss advances in bispecific antibody formats designed to enhance efficacy and reduce toxicity, alongside emerging therapeutic combinations. Our synthesis highlights the complexity of targeting myeloid malignancies while sparing normal hematopoietic cells. These insights underscore the potential of refined T-BsAb approaches to improve treatment specificity and efficacy in AML and related disorders, informing future therapeutic strategies and clinical development.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102772"},"PeriodicalIF":10.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oscar Wong, Zhijie Zheng, Mingbang Wang, Aihua Cao, Francis K L Chan, Siew C Ng, Qi Su
{"title":"Microbiome biomarkers in autism spectrum disorder: Toward prediction, diagnosis, and prognosis.","authors":"Oscar Wong, Zhijie Zheng, Mingbang Wang, Aihua Cao, Francis K L Chan, Siew C Ng, Qi Su","doi":"10.1016/j.xcrm.2026.102780","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102780","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a heterogeneous condition that lacks objective diagnostic biomarkers, often resulting in delayed intervention. Evidence increasingly links gut microbiota dysregulation to ASD pathophysiology via the microbiota-gut-brain axis, suggesting plausible translational applications. This review outlines mechanistic insights from preclinical and clinical studies to illustrate how microbial disturbances affect neurodevelopment. It examines the evolution of biomarker research from early 16S rRNA sequencing to advanced shotgun metagenomics incorporating functional integration, multi-omics, and genomic variants. Such advancements enhance diagnostic accuracy and generalizability. Although clinical causal evidence remains indirect, these microbial signatures show potential for early diagnosis, presymptomatic risk prediction, and tailored therapies. Key challenges include prospective validation in diverse cohorts, specificity testing against comorbidities, and addressing clinical heterogeneity. By summarizing methodological gaps and providing future guidance, this review aims to bridge mechanistic research and clinical practice to improve outcomes across the spectrum.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102780"},"PeriodicalIF":10.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Ling, Shihua Yang, Xianbao Shi, Zhenguo Cheng, Wei Wang, Meng Niu, Funan Liu, Jin Sun, Mengchi Sun
{"title":"An inhalable microbe-oncolytic virus consortium for lung cancer treatment.","authors":"Hao Ling, Shihua Yang, Xianbao Shi, Zhenguo Cheng, Wei Wang, Meng Niu, Funan Liu, Jin Sun, Mengchi Sun","doi":"10.1016/j.xcrm.2026.102771","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102771","url":null,"abstract":"<p><p>Oncolytic viruses (OVs) represent a promising cancer therapy due to their selective cytotoxicity, yet clinical success in lung cancer is hindered by biological barriers and immunosuppressive microenvironments. To address these barriers, an inhalable microbe-OVs consortium is developed by conjugating tumor-responsive PEGylated adenoviruses (Ads) to motile algae (Synechococcus WH8102) via click chemistry. Driven by algal motility, the consortium penetrates respiratory mucus and epithelial barriers to reach lung tumor sites. Intratumoral calcium ion deprivation by the algae disrupts cellular tight junctions and facilitates deep penetration into solid tumors, thereby potentiating Ads-mediated immunogenic cell death (ICD) and boosting microbial and viral co-activated antitumor immunity. Inhalation administration demonstrates robust antitumor effectiveness in murine lung tumor. This inhalable microbe-OV strategy provides a promising scheme for clinical oncolytic microorganism biotherapeutics.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102771"},"PeriodicalIF":10.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haoxiang Yuan, Bo Zeng, Pu Shen, Jiancheng Deng, Ying Chen, Meiyu Huang, Wentao Wu, Xin Xu, Xuanlin Zhang, Xue Liu, Xudong Zhang, Zhijin Fan, Jianxing He
{"title":"Macrophage-mimetic photothermal nanotherapeutics regulate mitochondrial homeostasis and inflammatory cascades in lung ischemia-reperfusion injury.","authors":"Haoxiang Yuan, Bo Zeng, Pu Shen, Jiancheng Deng, Ying Chen, Meiyu Huang, Wentao Wu, Xin Xu, Xuanlin Zhang, Xue Liu, Xudong Zhang, Zhijin Fan, Jianxing He","doi":"10.1016/j.xcrm.2026.102768","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102768","url":null,"abstract":"<p><p>Pulmonary ischemia-reperfusion injury is a major cause of acute lung injury and primary graft dysfunction after lung transplantation, with few effective treatments available. In this study, we develop a macrophage-membrane-coated mesoporous polydopamine nanoparticle system loaded with ginsenoside Rg3 (Rg3@PACVs) and activated by near-infrared irradiation. This design enables precise targeting of injured lung tissue via chemokine-receptor- and integrin-mediated pathways, while allowing controllable, on-demand drug release. In vitro hypoxia-reoxygenation models and a rat pulmonary ischemia-reperfusion model demonstrate that Rg3@PACVs with mild photothermal therapy reduce reactive oxygen species accumulation, suppress inflammatory cytokines, preserve mitochondrial structure and tricarboxylic acid cycle metabolism, and alleviate tissue injury. The approach combines targeted delivery, multimodal protection against oxidative and inflammatory damage, and mitochondrial restoration. These findings suggest a promising therapeutic strategy for mitigating lung ischemia-reperfusion injury and potentially for other inflammation- and oxidative-stress-driven pulmonary diseases.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102768"},"PeriodicalIF":10.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omid Hajihassani, Asael Roichman, Jacob A Boyer, Michal MacArthur, Ricardo Cordova, Alexander Loftus, Christina S Boutros, Jonathan J Hue, Parnian Naji, Soubhi Tahhan, Peter Gallagher, William Beegan, Danyal Shah, James Choi, Nimat Manzoor, Shihong Lei, Christine Kim, Moeez Rathore, Ishan Shah, Kevin Lebo, Helen Cheng, Anusha Mudigonda, Craig Hunter, Mehrdad Zarei, Sydney Alibeckoff, Karen Ji, Hallie Graor, Masaru Miyagi, Ali Vaziri-Gohar, Henri Brunengraber, Rui Wang, Peder J Lund, Luke D Rothermel, Joshua D Rabinowitz, Jordan M Winter
{"title":"A ketogenic diet sensitizes pancreatic cancer to glutamine metabolism inhibitors.","authors":"Omid Hajihassani, Asael Roichman, Jacob A Boyer, Michal MacArthur, Ricardo Cordova, Alexander Loftus, Christina S Boutros, Jonathan J Hue, Parnian Naji, Soubhi Tahhan, Peter Gallagher, William Beegan, Danyal Shah, James Choi, Nimat Manzoor, Shihong Lei, Christine Kim, Moeez Rathore, Ishan Shah, Kevin Lebo, Helen Cheng, Anusha Mudigonda, Craig Hunter, Mehrdad Zarei, Sydney Alibeckoff, Karen Ji, Hallie Graor, Masaru Miyagi, Ali Vaziri-Gohar, Henri Brunengraber, Rui Wang, Peder J Lund, Luke D Rothermel, Joshua D Rabinowitz, Jordan M Winter","doi":"10.1016/j.xcrm.2026.102770","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102770","url":null,"abstract":"<p><p>Pancreatic cancer is the third leading cause of cancer-related death in the United States. Current chemotherapy options provide limited benefits. Emerging evidence suggests that a ketogenic diet (KD) exerts anti-tumor effects by reprogramming tumor metabolism and revealing therapeutic vulnerabilities. Efforts to target glutamine metabolism-an essential pathway in many cancers-have shown promise in preclinical models, but clinical efficacy has remained limited. Here, we show that a KD increases tricarboxylic acid (TCA) cycle activity and elevates reliance on glutamine-related metabolites in murine pancreatic cancer models and in vitro under KD-mimicking conditions. This metabolic adaptation occurs in response to reduced glucose availability. We demonstrate that combining glutamine metabolism inhibitors, such as CB-839 or 6-diazo-5-oxo-L-norleucine (DON), with a KD leads to robust anti-tumor effects in preclinical models of pancreatic cancer. Thus, metabolic vulnerability induced by dietary intervention provides a rationale for combining glutamine-targeted therapies with a ketogenic diet in future clinical studies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102770"},"PeriodicalIF":10.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan H Sussman, Derek A Oldridge, Wenbao Yu, Chia-Hui Chen, Abigail M Zellmer, Jiazhen Rong, Arianne Parvaresh-Rizi, Anusha Thadi, Austin Yang, Joseph S Tumulty, Barbara Xiong, David W Wu, Yusha Sun, Shovik Bandyopadhyay, Jason Xu, Stephanie Brosius, Una Yamamoto Barkardottir, Isabelle Seka, Kyung Jin Ahn, Omar Elghawy, Amy E Baxter, Mateusz P Koptyra, Rami S Vanguri, Stephanie McGrory, Phillip B Storm, Nduka M Amankulor, Mariarita Santi, Angela N Viaene, Nancy Zhang, Thomas De Raedt, Kristina Cole, Kai Tan
{"title":"A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.","authors":"Jonathan H Sussman, Derek A Oldridge, Wenbao Yu, Chia-Hui Chen, Abigail M Zellmer, Jiazhen Rong, Arianne Parvaresh-Rizi, Anusha Thadi, Austin Yang, Joseph S Tumulty, Barbara Xiong, David W Wu, Yusha Sun, Shovik Bandyopadhyay, Jason Xu, Stephanie Brosius, Una Yamamoto Barkardottir, Isabelle Seka, Kyung Jin Ahn, Omar Elghawy, Amy E Baxter, Mateusz P Koptyra, Rami S Vanguri, Stephanie McGrory, Phillip B Storm, Nduka M Amankulor, Mariarita Santi, Angela N Viaene, Nancy Zhang, Thomas De Raedt, Kristina Cole, Kai Tan","doi":"10.1016/j.xcrm.2026.102766","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102766","url":null,"abstract":"<p><p>Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities with adult glioma, it comprises distinct disease entities. In this study, we longitudinally profile a molecularly diverse cohort of 16 pHGG patients through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of neoplastic and microenvironmental features during disease progression and treatment. We define a set of core pHGG neoplastic cell states and observe differential tumor-myeloid interactions between malignant cell phenotypes. We find that essential neuromodulators and the interferon response are upregulated post-therapy, implicating them as malignant cell-intrinsic targets. We observe an increase in oligodendrocytes upon progression and that they coordinate spatial motifs with proneural tumor cells. This multiomic atlas of longitudinal pHGG captures features of therapy response and provides a scalable reference for the study of pediatric brain tumors.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102766"},"PeriodicalIF":10.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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