Cancer CellPub Date : 2025-05-15DOI: 10.1016/j.ccell.2025.04.013
Derek Dang, Akash Deogharkar, John McKolay, Kyle S. Smith, Pooja Panwalkar, Simon Hoffman, Wentao Tian, Sunjong Ji, Ana P. Azambuja, Siva Kumar Natarajan, Joanna Lum, Jill Bayliss, Katie Manzeck, Stefan R. Sweha, Erin Hamanishi, Matthew Pun, Diya Patel, Sagar Rau, Olamide Animasahun, Abhinav Achreja, Sriram Venneti
{"title":"Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis","authors":"Derek Dang, Akash Deogharkar, John McKolay, Kyle S. Smith, Pooja Panwalkar, Simon Hoffman, Wentao Tian, Sunjong Ji, Ana P. Azambuja, Siva Kumar Natarajan, Joanna Lum, Jill Bayliss, Katie Manzeck, Stefan R. Sweha, Erin Hamanishi, Matthew Pun, Diya Patel, Sagar Rau, Olamide Animasahun, Abhinav Achreja, Sriram Venneti","doi":"10.1016/j.ccell.2025.04.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.013","url":null,"abstract":"MYC-driven group-3 medulloblastomas (MBs) are malignant pediatric brain cancers without cures. To define actionable metabolic dependencies, we identify upregulation of dihydrolipoyl transacetylase (DLAT), the E2-subunit of pyruvate dehydrogenase complex (PDC) in a subset of group-3 MB with poor prognosis. DLAT is induced by c-MYC and targeting DLAT lowers TCA cycle metabolism and glutathione synthesis. We also note upregulation of isocitrate dehydrogenase 1 (IDH1) gene expression in group-3 MB patient tumors and suppression of IDH1 epigenetically reduces c-MYC and downstream DLAT levels in multiple c-MYC amplified cancers. DLAT is a central regulator of cuproptosis (copper-dependent cell death) induced by the copper ionophore elesclomol. DLAT expression in group-3 MB cells correlates with increased sensitivity to cuproptosis. Elesclomol is brain-penetrant and suppresses tumor growth <em>in vivo</em> in multiple group-3 MB animal models. Our data uncover an IDH1/c-MYC dependent vulnerability that regulates DLAT levels and can be targeted to kill group-3 MB by cuproptosis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"145 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980019","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}
Cancer CellPub Date : 2025-05-12DOI: 10.1016/j.ccell.2025.04.012
Monika Julia Wolf, Alexandra Hoos, Judith Bauer, Steffen Boettcher, Markus Knust, Achim Weber, Nicole Simonavicius, Christoph Schneider, Matthias Lang, Michael Stürzl, Roland S. Croner, Andreas Konrad, Markus G. Manz, Holger Moch, Adriano Aguzzi, Geert van Loo, Manolis Pasparakis, Marco Prinz, Lubor Borsig, Mathias Heikenwalder
{"title":"Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway","authors":"Monika Julia Wolf, Alexandra Hoos, Judith Bauer, Steffen Boettcher, Markus Knust, Achim Weber, Nicole Simonavicius, Christoph Schneider, Matthias Lang, Michael Stürzl, Roland S. Croner, Andreas Konrad, Markus G. Manz, Holger Moch, Adriano Aguzzi, Geert van Loo, Manolis Pasparakis, Marco Prinz, Lubor Borsig, Mathias Heikenwalder","doi":"10.1016/j.ccell.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.012","url":null,"abstract":"(Cancer Cell <em>22</em>, 91–105; July 10, 2012)","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"51 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933505","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}
Cancer CellPub Date : 2025-05-12DOI: 10.1016/j.ccell.2025.04.008
Tian V. Tian, Silvia Affò
{"title":"Stromal barriers to the abscopal effect","authors":"Tian V. Tian, Silvia Affò","doi":"10.1016/j.ccell.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.008","url":null,"abstract":"In this issue of <em>Cancer Cell</em>, Zhang et al. reveal that PAI-1-induced SFRP2<sup>high</sup> cancer-associated fibroblasts reduce the abscopal effect of radioimmunotherapy. Targeting PAI-1 or SFRP2 enhances T cell recruitment and prevents the formation of an immunosuppressive perivascular niche, improving radioimmunotherapy’s abscopal effect.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"8 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933503","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}
Cancer CellPub Date : 2025-05-08DOI: 10.1016/j.ccell.2025.04.007
Hannah Garner, Moreno Martinovic, Ning Qing Liu, Noor A.M. Bakker, Irene Querol Velilla, Cheei-Sing Hau, Kim Vrijland, Daphne Kaldenbach, Marleen Kok, Elzo de Wit, Karin E. de Visser
{"title":"Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread","authors":"Hannah Garner, Moreno Martinovic, Ning Qing Liu, Noor A.M. Bakker, Irene Querol Velilla, Cheei-Sing Hau, Kim Vrijland, Daphne Kaldenbach, Marleen Kok, Elzo de Wit, Karin E. de Visser","doi":"10.1016/j.ccell.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.007","url":null,"abstract":"Tumor-induced systemic accumulation and polarization of neutrophils to an immunosuppressive phenotype is a potent driver of metastasis formation. Yet, how mammary tumors reprogram granulopoiesis at the molecular level and when tumor imprinting occurs during neutrophil development remains underexplored. Here, we combined single-cell, chromatin and functional analyses to unravel the tumor-driven reprogramming of granulopoiesis in the bone marrow, along with intervention studies aimed at reversing this process. We observe that mammary tumors accelerate commitment to the neutrophil lineage at the expense of lymphopoiesis and erythropoiesis without stimulating the development of a novel myeloid lineage. Moreover, tumor-directed immunosuppressive imprinting of neutrophils starts early in hematopoiesis. Treatment with anti-IL-1β normalizes tumor-induced granulopoiesis, reducing neutrophil immunosuppressive phenotype and mitigating metastatic spread. Together, these data provide molecular insights into the aberrant, tumor-driven neutrophil differentiation pathway leading to metastasis-promoting chronic inflammation and how it can be reversed to reduce metastatic spread.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"49 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920769","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}
{"title":"Immune evolution in pre-invasive lung adenocarcinoma","authors":"Adithya Balasubramanian, Marie-Liesse Asselin-Labat","doi":"10.1016/j.ccell.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.005","url":null,"abstract":"The mechanisms governing the progression of precursor lesions to invasive lung adenocarcinoma (LUAD) remain poorly understood. In this issue of <em>Cancer Cell</em>, Zhu et al. map the dynamic immune changes associated with this progression using high-resolution spatial mapping. Their identification of TIM-3 as a potential target may shift strategies for LUAD immunoprevention.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"53 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920767","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}
Cancer CellPub Date : 2025-05-08DOI: 10.1016/j.ccell.2025.04.006
Elina Timosenko, Dmitry I. Gabrilovich
{"title":"Regulating the fate of tumor-associated macrophages","authors":"Elina Timosenko, Dmitry I. Gabrilovich","doi":"10.1016/j.ccell.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.006","url":null,"abstract":"Tumor-associated macrophages (TAMs) are key players in tumor progression, yet their role in this process remains only partially understood. In this issue of <em>Cancer Cell</em>, Sheban et al. demonstrate that zinc finger E-box-binding homeobox 2 (ZEB2) acts as a master regulator that reprograms TAMs toward a pro-tumor phenotype and that therapeutic targeting of ZEB2 exhibits anti-tumor activity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"96 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920673","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}
{"title":"Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma","authors":"Shanshan Zhang, Yan Zhou, Zhonghua Liu, Yuqian Wang, Xiang Zhou, Haiwen Chen, Xinyu Zhang, Yanhong Chen, Qisheng Feng, Xiaoping Ye, Shanghang Xie, Mu-Sheng Zeng, Weiwei Zhai, Yi-Xin Zeng, Sumei Cao, Guideng Li, Miao Xu","doi":"10.1016/j.ccell.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.009","url":null,"abstract":"To identify nasopharyngeal carcinoma (NPC)-relevant T cell receptors (TCRs), we profile the repertoires of peripheral blood TCRβ chains from 228 NPC patients, 241 at-risk controls positive for serum Epstein-Barr virus (EBV) VCA-IgA antibody, and 251 seronegative controls. We develop a TCR-based signature (T-score) based on 208 NPC-enriched CDR3β sequences, which accurately diagnoses NPC in both the original and independent validation cohorts. Notably, a higher T-score, associated with a shorter time interval to NPC diagnosis, effectively identifies early-stage NPC among EBV-seropositive at-risk individuals prior to clinical diagnosis. These NPC-enriched TCRs react against not only EBV-specific antigens but also non-EBV antigens expressed by NPC cells, indicating a broad range of specificities. Moreover, the abundance of NPC-enriched CD8<sup>+</sup> T cells in blood correlates with the infiltration of non-exhausted T cell counterparts in tumors and predicts prolonged survival, suggesting that these NPC-enriched T cells have significant potential for disease monitoring and therapeutic applications.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"55 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920765","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}
Cancer CellPub Date : 2025-05-08DOI: 10.1016/j.ccell.2025.04.003
Bo Zhu, Pingjun Chen, Muhammad Aminu, Jian-Rong Li, Junya Fujimoto, Yanhua Tian, Lingzhi Hong, Hong Chen, Xin Hu, Chenyang Li, Natalie Vokes, Andre L. Moreira, Don L. Gibbons, Luisa M. Solis Soto, Edwin Roger Parra Cuentas, Ou Shi, Songhui Diao, Jie Ye, Frank R. Rojas, Eduardo Vilar, Jianjun Zhang
{"title":"Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception","authors":"Bo Zhu, Pingjun Chen, Muhammad Aminu, Jian-Rong Li, Junya Fujimoto, Yanhua Tian, Lingzhi Hong, Hong Chen, Xin Hu, Chenyang Li, Natalie Vokes, Andre L. Moreira, Don L. Gibbons, Luisa M. Solis Soto, Edwin Roger Parra Cuentas, Ou Shi, Songhui Diao, Jie Ye, Frank R. Rojas, Eduardo Vilar, Jianjun Zhang","doi":"10.1016/j.ccell.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.003","url":null,"abstract":"How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. <em>In vivo</em> TIM-3 blockade at precancer stage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These results highlight the coordination of innate and adaptive immune response/evasion during LUAD precancer evolution and suggest TIM-3 as a potential target for LUAD precancer interception.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"36 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920766","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}
Cancer CellPub Date : 2025-05-08DOI: 10.1016/j.ccell.2025.04.011
Michael Schulz, Marco Prinz
{"title":"Brain metastasis: From etiology to ecotypes","authors":"Michael Schulz, Marco Prinz","doi":"10.1016/j.ccell.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.011","url":null,"abstract":"Despite recent advances in anti-cancer therapies, metastasis, especially to the brain, represents a major clinical challenge with rising incidences. In this issue of <em>Cancer Cell</em>, Xing et al. present a comprehensive transcriptomic map of the metastatic brain tumor environment at single-cell resolution.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"64 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920686","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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