Cancer Cell最新文献_第3页

Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity 微生物癌症免疫疗法重新编程造血以增强髓细胞驱动的抗肿瘤免疫

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-29 DOI: 10.1016/j.ccell.2025.05.002

Andrew W. Daman, Anthony C. Antonelli, Gil Redelman-Sidi, Lucinda Paddock, Shireen Khayat, Mythili Ketavarapu, Jin Gyu Cheong, Leonardo F. Jurado, Anna Benjamin, Song Jiang, Dughan Ahimovic, Victoria R. Lawless, Michael J. Bale, Oleg Loutochin, Victor A. McPherson, Maziar Divangahi, Rachel E. Niec, Dana Pe’er, Eugene Pietzak, Steven Z. Josefowicz, Michael S. Glickman

{"title":"Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity","authors":"Andrew W. Daman, Anthony C. Antonelli, Gil Redelman-Sidi, Lucinda Paddock, Shireen Khayat, Mythili Ketavarapu, Jin Gyu Cheong, Leonardo F. Jurado, Anna Benjamin, Song Jiang, Dughan Ahimovic, Victoria R. Lawless, Michael J. Bale, Oleg Loutochin, Victor A. McPherson, Maziar Divangahi, Rachel E. Niec, Dana Pe’er, Eugene Pietzak, Steven Z. Josefowicz, Michael S. Glickman","doi":"10.1016/j.ccell.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.05.002","url":null,"abstract":"Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder colonizes the bone marrow and, in both mice and humans, reprograms HSPCs to alter and amplify myelopoiesis. BCG-reprogrammed HSPCs are sufficient to confer augmented anti-tumor immunity through production of neutrophils, monocytes, and dendritic cells that broadly remodel the tumor microenvironment, drive T cell-dependent anti-tumor responses, and synergize with checkpoint blockade. We conclude that bladder BCG acts systemically through hematopoiesis, highlighting the broad potential of HSPC reprogramming to enhance the innate drivers of T cell-dependent tumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"29 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165271","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}

引用次数: 0

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma 在胶质母细胞瘤中，癌细胞和免疫细胞之间的相互作用驱动过渡到间充质样状态

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-27 DOI: 10.1016/j.ccell.2025.05.007

Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson, Chad Myskiw, Lyla Atta, Lillian Bussema, Stephen W. Eichhorn, Alissa C. Greenwald, Gabriela S. Kinker, Christopher Rodman, L. Nicolas Gonzalez Castro, Hiroaki Wakimoto, Orit Rozenblatt-Rosen, Xiaowei Zhuang, Jean Fan, Tony Hunter, Inder M. Verma, Kai W. Wucherpfennig, Aviv Regev, Mario L. Suvà, Itay Tirosh

引用次数: 0

Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target elp1相关Sonic hedgehog髓母细胞瘤的遗传模型确定MDM2为选择性治疗靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-15 DOI: 10.1016/j.ccell.2025.04.014

Shiekh Tanveer Ahmad, Yiran Li, Jesus Garcia-Lopez, Brian L. Gudenas, Jennifer Hadley, Leena Paul, Stephanie C. Wu, Alaa Refaat, Marija Kojic, Melissa Batts, Taha Soliman, Aaron Pitre, Frederik Arnskötter, Frederique Zindy, Alun Jones, Nathaniel R. Twarog, Anand Mayasundari, Brandon Bianski, Christopher Tinkle, Abbas Shirinifard, Paul A. Northcott

{"title":"Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target","authors":"Shiekh Tanveer Ahmad, Yiran Li, Jesus Garcia-Lopez, Brian L. Gudenas, Jennifer Hadley, Leena Paul, Stephanie C. Wu, Alaa Refaat, Marija Kojic, Melissa Batts, Taha Soliman, Aaron Pitre, Frederik Arnskötter, Frederique Zindy, Alun Jones, Nathaniel R. Twarog, Anand Mayasundari, Brandon Bianski, Christopher Tinkle, Abbas Shirinifard, Paul A. Northcott","doi":"10.1016/j.ccell.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.014","url":null,"abstract":"Germline loss-of-function (LOF) variants in Elongator acetyltransferase complex subunit 1 (ELP1) are the most prevalent predisposing genetic events in childhood medulloblastoma (MB), accounting for ∼30% of the Sonic hedgehog (SHH) 3 subtype. The mechanism(s) by which germline ELP1 deficiency provokes SHH-MB pathogenesis remain unknown. Genetically engineered mice mimicking heterozygous Elp1 LOF (Elp1HET) seen in affected germline carriers exhibit hallmark features of premalignancy in cerebellar granule neuron progenitors (GNPs), including increased DNA replication stress, genomic instability, accelerated cell cycle, and stalled differentiation. Orthotopic transplantation of Elp1HET GNPs harboring somatic Ptch1 inactivation yields SHH-MB-like tumors with compromised p53 signaling, providing a plausible explanation for the exclusivity of ELP1-associated MBs in the SHH-3 subtype. Preclinical treatment of ELP1-mutant patient-derived xenografts with an FDA-approved MDM2 inhibitor reactivates p53-dependent apoptosis and extends survival. Our findings functionally substantiate the role of ELP1 deficiency in SHH-MB predisposition and nominate therapeutics targeting MDM2 as a rational treatment option.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"13 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980018","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}

引用次数: 0

Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis 异柠檬酸脱氢酶1启动组-3髓母细胞瘤治疗铜增生

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-15 DOI: 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 in vivo 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}

引用次数: 0

Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway 结肠癌细胞诱导内皮细胞CCR2信号通过JAK2-Stat5和p38MAPK途径实现外渗

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-12 DOI: 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

引用次数: 0

Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer 化疗期间获得性半鳞片化提示分化是膀胱癌的治疗策略

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-12 DOI: 10.1016/j.ccell.2025.04.010

Manli Wang, Xuelan Chen, Ping Tan, Yiyun Wang, Xiangyu Pan, Tianhai Lin, Yong Jiang, Bo Wang, Huan Xu, Yuying Wang, Yucen Yang, Jian Wang, Lei Zhao, Jiapeng Zhang, Ailing Zhong, Yiman Peng, Jiajia Du, Qi Zhang, Jianan Zheng, Jingyao Chen, Chong Chen

引用次数: 0

Stromal barriers to the abscopal effect 基质屏障对体外效应的影响

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-12 DOI: 10.1016/j.ccell.2025.04.008

Tian V. Tian, Silvia Affò

引用次数: 0

Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread 了解和逆转乳腺肿瘤驱动的骨髓生成重编程以减少转移性扩散

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 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}

引用次数: 0

Regulating the fate of tumor-associated macrophages 调节肿瘤相关巨噬细胞的命运

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 10.1016/j.ccell.2025.04.006

Elina Timosenko, Dmitry I. Gabrilovich

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Immune evolution in pre-invasive lung adenocarcinoma 侵袭前肺腺癌的免疫进化

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 10.1016/j.ccell.2025.04.005

Adithya Balasubramanian, Marie-Liesse Asselin-Labat

引用次数: 0