Cancer Cell最新文献_第7页

Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion 癌细胞衍生的精氨酸在肿瘤相关巨噬细胞中促进多胺生物合成以促进免疫逃逸

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.015

Yinghua Zhu, Ziwei Zhou, Xin Du, Xiaorong Lin, Zhi-Mei Liang, Si Chen, Yiwei Sun, Yue Wang, Zhenkun Na, Zhiyong Wu, Jiaxin Zhong, Beinan Han, Xiangping Zhu, Wenkui Fu, Hongde Li, Man-Li Luo, Hai Hu

{"title":"Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion","authors":"Yinghua Zhu, Ziwei Zhou, Xin Du, Xiaorong Lin, Zhi-Mei Liang, Si Chen, Yiwei Sun, Yue Wang, Zhenkun Na, Zhiyong Wu, Jiaxin Zhong, Beinan Han, Xiangping Zhu, Wenkui Fu, Hongde Li, Man-Li Luo, Hai Hu","doi":"10.1016/j.ccell.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.015","url":null,"abstract":"Arginine metabolism reshapes the tumor microenvironment (TME) into a pro-tumor niche through complex metabolic cross-feeding among various cell types. However, the key intercellular metabolic communication that mediates the collective effects of arginine metabolism within the TME remains unclear. Here, we reveal that the metabolic interplay between cancer cells and macrophages plays a dominant role in arginine-driven breast cancer progression. Within the TME, breast cancer cells serve as the primary source of arginine, which induces a pro-tumor polarization of tumor-associated macrophages (TAMs), thereby suppressing the anti-tumor activity of CD8+ T cells. Notably, this cancer cell-macrophage interaction overrides the arginine-mediated enhancement of CD8+ T cell anti-tumor activity. Mechanistically, polyamines derived from arginine metabolism enhance pro-tumor TAM polarization via thymine DNA glycosylase (TDG)-mediated DNA demethylation, regulated by p53 signaling. Importantly, targeting the arginine-polyamine-TDG axis between cancer cells and macrophages significantly suppresses breast cancer growth, highlighting its therapeutic potential.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"216 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766922","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

Advocating for change—Integration of efforts across the drug discovery and development continuum 倡导变革——整合整个药物发现和开发连续体的努力

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.009

Timothy P. Heffernan, Giulio F. Draetta

引用次数: 0

Translation dysregulation in cancer as a source for targetable antigens 翻译失调在癌症中作为靶向抗原的来源

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.003

Chen Weller, Osnat Bartok, Christopher S. McGinnis, Heyilimu Palashati, Tian-Gen Chang, Dmitry Malko, Merav D. Shmueli, Asuteka Nagao, Deborah Hayoun, Ayaka Murayama, Yuriko Sakaguchi, Panagiotis Poulis, Aseel Khatib, Bracha Erlanger Avigdor, Sagi Gordon, Sapir Cohen Shvefel, Marie J. Zemanek, Morten M. Nielsen, Sigalit Boura-Halfon, Shira Sagie, Yardena Samuels

{"title":"Translation dysregulation in cancer as a source for targetable antigens","authors":"Chen Weller, Osnat Bartok, Christopher S. McGinnis, Heyilimu Palashati, Tian-Gen Chang, Dmitry Malko, Merav D. Shmueli, Asuteka Nagao, Deborah Hayoun, Ayaka Murayama, Yuriko Sakaguchi, Panagiotis Poulis, Aseel Khatib, Bracha Erlanger Avigdor, Sagi Gordon, Sapir Cohen Shvefel, Marie J. Zemanek, Morten M. Nielsen, Sigalit Boura-Halfon, Shira Sagie, Yardena Samuels","doi":"10.1016/j.ccell.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.003","url":null,"abstract":"Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized as foreign by T cells. Protein synthesis in malignant cells is dysregulated, which may result in the generation and presentation of aberrant peptides that can be exploited for T cell-based therapies. To investigate the role of translational dysregulation in immunological tumor control, we disrupt translation fidelity by deleting tRNA wybutosine (yW)-synthesizing protein 2 (TYW2) in tumor cells and characterize the downstream impact on translation fidelity and immunogenicity using immunopeptidomics, genomics, and functional assays. These analyses reveal that TYW2 knockout (KO) cells generate immunogenic out-of-frame peptides. Furthermore, Tyw2 loss increases tumor immunogenicity and leads to anti-programmed cell death 1 (PD-1) checkpoint blockade sensitivity in vivo. Importantly, reduced TYW2 expression is associated with increased response to checkpoint blockade in patients. Together, we demonstrate that defects in translation fidelity drive tumor immunogenicity and may be leveraged for cancer immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"3 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713596","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

A niche driven mechanism determines response and a mutation-independent therapeutic approach for myeloid malignancies 一个利基驱动的机制决定了骨髓恶性肿瘤的反应和一种不依赖突变的治疗方法

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.007

Ioanna Mosialou, Abdullah M. Ali, Rossella Labella, Brygida Bisikirska, Alvaro Cuesta-Dominguez, Paraskevi Vgenopoulou, Ismarc Reyes, Sanjana M. Rao, Anqi Wang, Na Luo, Marta Galan-Diez, Junfei Zhao, Brian J. Chernak, Jan Philipp Bewersdorf, Kazuya Fukasawa, Jiayu Su, Jason Higa, Rachel A. Adams, Adam L. Corper, Sergey Pampou, Stavroula Kousteni

{"title":"A niche driven mechanism determines response and a mutation-independent therapeutic approach for myeloid malignancies","authors":"Ioanna Mosialou, Abdullah M. Ali, Rossella Labella, Brygida Bisikirska, Alvaro Cuesta-Dominguez, Paraskevi Vgenopoulou, Ismarc Reyes, Sanjana M. Rao, Anqi Wang, Na Luo, Marta Galan-Diez, Junfei Zhao, Brian J. Chernak, Jan Philipp Bewersdorf, Kazuya Fukasawa, Jiayu Su, Jason Higa, Rachel A. Adams, Adam L. Corper, Sergey Pampou, Stavroula Kousteni","doi":"10.1016/j.ccell.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.007","url":null,"abstract":"Myeloid cancers such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) remain resistant to standard of care (SOC) and targeted therapies. In this study, we demonstrate that responsiveness to therapy is associated with activation of β-catenin-JAG1 in osteoblastic cells of patients treated with all-trans-retinoic acid (ATRA). ATRA suppresses β-catenin activity in patients and leukemic mice. Consequently, it inhibits the growth and survival of MDS/AML cells from patients with active β-catenin-JAG1 signaling and promotes their differentiation. This occurs independently of cytogenetics and mutational profile. ATRA also improves disease outcome in mice with no evidence of relapse and a superior safety profile to SOC. A human anti-JAG1 antibody improves efficacy in leukemic mice and patient-derived MDS/AML cells. β-catenin activation provides an explanation for the differential response to ATRA and a mechanistic biomarker for ATRA repurposing in myeloid malignancies, potentially evading relapse and extending across a broad range of cancers.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"33 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713602","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

The discrete charm of oncolytic viruses: Toward the finish line 溶瘤病毒的独特魅力：冲向终点线

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.010

Pedro R. Lowenstein, Maria Luisa Varela, Maria G. Castro

引用次数: 0

All-trans retinoic acid beyond acute promyelocytic leukemia 全反式维甲酸治疗急性早幼粒细胞白血病

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.008

Usama-Ur Rehman, Michael Lübbert

引用次数: 0

Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics 单细胞空间多组学揭示癌症相关成纤维细胞的保守空间亚型和细胞邻域

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.004

Yunhe Liu, Ansam Sinjab, Jimin Min, Guangchun Han, Francesca Paradiso, Yuanyuan Zhang, Ruiping Wang, Guangsheng Pei, Yibo Dai, Yang Liu, Kyung Serk Cho, Enyu Dai, Akshay Basi, Jared K. Burks, Kimal I. Rajapakshe, Yanshuo Chu, Jiahui Jiang, Daiwei Zhang, Xinmiao Yan, Paola A. Guerrero, Linghua Wang

{"title":"Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics","authors":"Yunhe Liu, Ansam Sinjab, Jimin Min, Guangchun Han, Francesca Paradiso, Yuanyuan Zhang, Ruiping Wang, Guangsheng Pei, Yibo Dai, Yang Liu, Kyung Serk Cho, Enyu Dai, Akshay Basi, Jared K. Burks, Kimal I. Rajapakshe, Yanshuo Chu, Jiahui Jiang, Daiwei Zhang, Xinmiao Yan, Paola A. Guerrero, Linghua Wang","doi":"10.1016/j.ccell.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.004","url":null,"abstract":"Cancer-associated fibroblasts (CAFs) are a multifaceted cell population essential for shaping the tumor microenvironment (TME) and influencing therapy responses. Characterizing the spatial organization and interactions of CAFs within complex tissue environments provides critical insights into tumor biology and immunobiology. In this study, through integrative analyses of over 14 million cells from 10 cancer types across 7 spatial transcriptomics and proteomics platforms, we discover, validate, and characterize four distinct spatial CAF subtypes. These subtypes are conserved across cancer types and independent of spatial omics platforms. Notably, they exhibit distinct spatial organizational patterns, neighboring cell compositions, interaction networks, and transcriptomic profiles. Their abundance and composition vary across tissues, shaping TME characteristics, such as levels, distribution, and state composition of tumor-infiltrating immune cells, tumor immune phenotypes, and patient survival. This study enriches our understanding of CAF spatial heterogeneity in cancer and paves the way for novel approaches to target and modulate CAFs.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"1 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713597","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

Leveraging real-world data to advance biomarker discovery and precision oncology 利用真实世界的数据来推进生物标志物的发现和精确肿瘤学

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.012

Jiaqian Luo, David B. Solit

引用次数: 0

Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy 为免疫检查点抑制剂治疗导航已建立的和新兴的生物标志物

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-03-27 DOI: 10.1016/j.ccell.2025.03.006

Stephen L. Wang, Timothy A. Chan

引用次数: 0

Neoadjuvant immune checkpoint therapy: Enabling insights into fundamental human immunology and clinical benefit 新辅助免疫检查点治疗：使洞察基本的人类免疫学和临床效益