Cancer Cell最新文献_第8页

Diet-microbiome interactions in cancer 饮食-微生物组在癌症中的相互作用

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.013

Suhaib K. Abdeen, Ignacio Mastandrea, Nina Stinchcombe, Jens Puschhof, Eran Elinav

{"title":"Diet-microbiome interactions in cancer","authors":"Suhaib K. Abdeen, Ignacio Mastandrea, Nina Stinchcombe, Jens Puschhof, Eran Elinav","doi":"10.1016/j.ccell.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.013","url":null,"abstract":"Diet impacts cancer in diverse manners. Multiple nutritional effects on tumors are mediated by dietary modulation of commensals, residing in mucosal surfaces and possibly also within the tumor microenvironment. Mechanistically understanding such diet-microbiome-host interactions may enable to develop precision nutritional interventions impacting cancer development, dissemination, and treatment responses. However, data-driven nutritional strategies integrating diet-microbiome interactions are infrequently incorporated into cancer prevention and treatment schemes. Herein, we discuss how dietary composition affects cancer-related processes through alterations exerted by specific nutrients and complex foods on the microbiome. We highlight how dietary timing, including time-restricted feeding, impacts microbial function in modulating cancer and its therapy. We review existing and experimental nutritional approaches aimed at enhancing microbiome-mediated cancer treatment responsiveness while minimizing adverse effects, and address challenges and prospects in integrating diet-microbiome interactions into precision oncology. Collectively, mechanistically understanding diet-microbiome-host interactomes may enable to achieve a personalized and microbiome-informed optimization of nutritional cancer interventions.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"16 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766916","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

Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures 空间转录组学揭示了色氨酸代谢限制肿瘤内三级淋巴样结构的成熟

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.011

Zhonghui Tang, Yinqi Bai, Qi Fang, Yuchen Yuan, Qianwen Zeng, Shuling Chen, Tianyi Xu, Jianyu Chen, Li Tan, Chunqing Wang, Qian Li, Jinpei Lin, Zhuoxuan Yang, Xia Wu, Guowei Shi, Ji Wang, Changjun Yin, Jianping Guo, Shiping Liu, Sui Peng, Ming Kuang

{"title":"Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures","authors":"Zhonghui Tang, Yinqi Bai, Qi Fang, Yuchen Yuan, Qianwen Zeng, Shuling Chen, Tianyi Xu, Jianyu Chen, Li Tan, Chunqing Wang, Qian Li, Jinpei Lin, Zhuoxuan Yang, Xia Wu, Guowei Shi, Ji Wang, Changjun Yin, Jianping Guo, Shiping Liu, Sui Peng, Ming Kuang","doi":"10.1016/j.ccell.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.011","url":null,"abstract":"Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates found in numerous cancers, often linked to enhanced immunotherapy responses and better clinical outcomes. However, the factors driving TLS maturation are not fully understood. Using near single-cell spatial transcriptomic mapping, we comprehensively profile TLSs under various maturation stages and their microenvironment in hepatocellular carcinoma (HCC). Based on their developmental trajectories, we classify immature TLSs into two groups: conforming and deviating TLSs. Our findings indicate that conforming TLSs, similar to mature TLSs, possess a niche function for immunotherapy responses, while deviating TLSs do not. We discover that the tryptophan-enriched metabolic microenvironment shaped by malignant cells contributes to the deviation of TLS maturation. Inhibiting tryptophan metabolism promotes intratumoral TLS maturation and enhances tumor control, synergizing with anti-PD-1 treatments. Therefore, promoting TLS maturation represents a potential strategy to improve antitumor responses and immunotherapy outcomes.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"10 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766921","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

Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups 非功能性胰腺神经内分泌肿瘤的蛋白质基因组学特征揭示了临床相关亚群

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.016

Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Xianjun Yu

{"title":"Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups","authors":"Shunrong Ji, Lihua Cao, Jing Gao, Yang Du, Zeng Ye, Xin Lou, Fen Liu, Yehan Zhang, Junfeng Xu, Xiaohan Shi, Huan Wang, Penghao Li, Yikai Li, Hongxu Chen, Zhicheng Yang, Suizhi Gao, Wuhu Zhang, Dan Huang, Shujuan Ni, Miaoyan Wei, Xianjun Yu","doi":"10.1016/j.ccell.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.016","url":null,"abstract":"The majority of neuroendocrine neoplasms in pancreas are non-functional pancreatic neuroendocrine tumors (NF-PanNETs), which exhibit a high occurrence of distant metastases with limited therapeutic options. Here, we perform a comprehensive molecular characterization of 108 NF-PanNETs through integrative analysis of genomic, transcriptomic, proteomic, and phosphoproteomic profiles. Proteogenomic analysis provides functional insights into the genomic driver alterations of NF-PanNETs, revealing a potential mediator of MEN1 alterations using Men1-conditional knockout mice. Machine-learning-based modeling uncovers a three-protein signature as an independent prognostic factor, which is validated by an independent external cohort. Proteomic and phosphoproteomic-based stratification identifies four subtypes with distinct molecular characteristics, immune microenvironments, and clinicopathological features. Drug screening using patient-derived tumor organoids identifies cyclin-dependent kinase (CDK) 5 and Calcium Voltage-Gated Channel Subunit Alpha1 D (CACNA1D) as ubiquitous and subtype-specific targets, respectively, with in vivo validation using xenograft models. Together, our proteogenomic analyses illustrate a comprehensive molecular landscape of NF-PanNETs, revealing biological insights and therapeutic vulnerabilities.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"133 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766926","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 Terry Fox Research Institute Marathon of Hope Cancer Centres Network: A pan-Canadian precision oncology initiative 泰瑞福克斯研究所马拉松希望癌症中心网络：一个泛加拿大精确肿瘤学倡议

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-03 DOI: 10.1016/j.ccell.2025.03.014

引用次数: 0

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