Cancer Cell最新文献_第4页

Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma 免疫测序鉴定鼻咽癌早期检测的T细胞反应的特征

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 10.1016/j.ccell.2025.04.009

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

{"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+ 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}

引用次数: 0

Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception 人类和小鼠肺腺癌前体的空间和多组学分析显示，TIM-3可能是癌前阻断的靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 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. In vivo 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}

引用次数: 0

Brain metastasis: From etiology to ecotypes 脑转移：从病因到生态型

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-08 DOI: 10.1016/j.ccell.2025.04.011

Michael Schulz, Marco Prinz

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TAMing immunity through an unexpected source 通过一个意想不到的来源驯服免疫

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-05-01 DOI: 10.1016/j.ccell.2025.04.004

Ian Vogel, Sagar P. Bapat

引用次数: 0

Ribosomal rebellion: When protein factories drive cancer progression 核糖体叛乱：当蛋白质工厂驱动癌症进展

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.035

Qiushuang Wu, Sohail F. Tavazoie

引用次数: 0

Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts 骨转移瘤通过产生骨桥蛋白的破骨细胞减少对检查点阻断免疫疗法的骨外反应

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.036

Jia-Nan Cheng, Zheng Jin, Chunxia Su, Tao Jiang, Xiaobin Zheng, Jinming Guo, Xingyi Li, Han Chu, Jia Jia, Qin Zhou, Xiaofang Ding, Yiwen Zhang, Shouxia Xu, Fancong Dong, Qiao Zhang, Xinxin Yang, Tao Yang, Xiaoming Cheng, Haoran Zha, Degao Chen, Bo Zhu

{"title":"Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts","authors":"Jia-Nan Cheng, Zheng Jin, Chunxia Su, Tao Jiang, Xiaobin Zheng, Jinming Guo, Xingyi Li, Han Chu, Jia Jia, Qin Zhou, Xiaofang Ding, Yiwen Zhang, Shouxia Xu, Fancong Dong, Qiao Zhang, Xinxin Yang, Tao Yang, Xiaoming Cheng, Haoran Zha, Degao Chen, Bo Zhu","doi":"10.1016/j.ccell.2025.03.036","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.036","url":null,"abstract":"Bone metastatic lesions typically associate with suboptimal responses to immune checkpoint blockade (ICB) therapies. In this study, we observed that across multiple clinical cohorts and a variety of mouse models, the presence of osseous metastases induces ICB resistance in extraosseous tumors. Mechanistically, this long-distance communication is mediated by osseous tumor-conditioned osteoclasts producing osteopontin (OPN). Through circulation, OPN reprograms the extraosseous tumor microenvironment and impairs T cell recruitment and differentiation of CD8+TCF1+ precursor cells, an essential population for ICB efficacy. In mice, ICB responsiveness is restored by αRANKL blockade of osteoclastogenesis, neutralization of OPN in circulation, or tissue-specific depletion of OPN in osteoclasts. Both the mode of action and therapeutic benefit were validated in clinical cohorts with the αRANKL-ICB combinatory regimen. These findings establish bone as a specific immunoregulatory organ exploited by tumor metastasis and suggest osteoclastogenesis as a promising target to improve ICB prognosis in patients with bone metastasis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"32 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866995","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

Easing cisplatin’s toll in nasopharyngeal carcinoma 缓解顺铂在鼻咽癌中的作用

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.03.034

Michael J. Dennis, Ravindra Uppaluri

引用次数: 0

Stromal lipid species dictate melanoma metastasis and tropism 基质脂质种类决定黑色素瘤的转移和趋向性

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.04.001

Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Amaya Virós

{"title":"Stromal lipid species dictate melanoma metastasis and tropism","authors":"Shilpa Gurung, Timothy Budden, Karthik Mallela, Benjamin Jenkins, Alex von Kriegsheim, Esperanza Manrique, David Millán-Esteban, Isabel Romero-Camarero, Fabio Amaral, Sarah Craig, Pedro Durao, Joanna Pozniak, Laura Stennett, Duncan Smith, Garry Ashton, Alex Baker, Kang Zeng, Gilbert Fruhwirth, Victoria Sanz-Moreno, Jair Marques, Amaya Virós","doi":"10.1016/j.ccell.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.001","url":null,"abstract":"Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are still incompletely understood. We show that abundant stromal lipids from young subcutaneous adipocytes, including phosphatidylcholines, are taken up by melanoma cells, where they upregulate melanoma PI3K-AKT signaling, fatty acid oxidation, oxidative phosphorylation (OXPHOS) leading to oxidative stress, resulting in decreased metastatic burden. High OXPHOS melanoma cells predominantly seed the lung and brain; decreasing oxidative stress with antioxidants shifts tropism from the lung to the liver. By contrast, the aged TME provides fewer total lipids but is rich in ceramides, leading to lower OXPHOS and high metastatic burden. Aged TME ceramides taken up by melanoma cells activate the S1P-STAT3-IL-6 signaling axis and promote liver tropism. Inhibiting OXPHOS in the young TME or blocking the IL-6 receptor in the aged TME reduces the age-specific patterns of metastasis imposed by lipid availability.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"14 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866997","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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KMT2C deficiency drives transdifferentiation of double-negative prostate cancer and confer resistance to AR-targeted therapy KMT2C缺陷驱动双阴性前列腺癌转分化并赋予对ar靶向治疗的抗性

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-24 DOI: 10.1016/j.ccell.2025.04.002

Jiacheng Guo, Ni Li, Qiuli Liu, Zongyao Hao, Guanghui Zhu, Xuege Wang, Hanling Wang, Qiang Pan, Beitao Xu, Ying Han, Guoying Zhang, Yannan Lian, Wei Zhang, Yongqiang Gu, Naiheng Lin, Xin Zeng, Zige Jin, Weihua Lan, Jun Jiang, Dong Gao, Jun Qin

{"title":"KMT2C deficiency drives transdifferentiation of double-negative prostate cancer and confer resistance to AR-targeted therapy","authors":"Jiacheng Guo, Ni Li, Qiuli Liu, Zongyao Hao, Guanghui Zhu, Xuege Wang, Hanling Wang, Qiang Pan, Beitao Xu, Ying Han, Guoying Zhang, Yannan Lian, Wei Zhang, Yongqiang Gu, Naiheng Lin, Xin Zeng, Zige Jin, Weihua Lan, Jun Jiang, Dong Gao, Jun Qin","doi":"10.1016/j.ccell.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.04.002","url":null,"abstract":"Double-negative prostate cancer (DNPC), characterized by an androgen receptor (AR)- and neuroendocrine-null phenotype, frequently emerges following androgen deprivation therapy (ADT). However, our understanding of the origins and regulatory mechanisms of DNPC remains limited. Here, we discover that tumors with KMT2C mutation or loss are highly susceptible to transitioning into DNPC following ADT. We clarify that DNPC primarily stems from luminal cell transdifferentiation rather than basal cell transformation. Antiandrogen treatment induces KMT2C binding at enhancers of a subset of AR-regulated genes, preserving the adenocarcinoma lineage. KMT2C maintains ASPP2 expression via enhancer-promoter communication post-AR inhibition, while its inactivation reduces ASPP2, triggering ΔNp63-dependent transdifferentiation. This DNPC transition maintains fatty acid (FA) synthesis through ΔNp63-mediated SREBP1c transactivation, fueling DNPC growth via HRAS palmitoylation and MAPK signaling activation. These findings highlight KMT2C as an epigenetic checkpoint against DNPC development and suggest the therapeutic potential of targeting fatty acid synthesis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"7 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866998","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

AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes 人工智能驱动的预测性生物标志物发现与对比学习，以改善临床试验结果

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.029

Gustavo Arango-Argoty, Damian E. Bikiel, Gerald J. Sun, Elly Kipkogei, Kaitlin M. Smith, Sebastian Carrasco Pro, Elizabeth Y. Choe, Etai Jacob

{"title":"AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes","authors":"Gustavo Arango-Argoty, Damian E. Bikiel, Gerald J. Sun, Elly Kipkogei, Kaitlin M. Smith, Sebastian Carrasco Pro, Elizabeth Y. Choe, Etai Jacob","doi":"10.1016/j.ccell.2025.03.029","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.029","url":null,"abstract":"Modern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, remains challenging. To address this, we present a neural network framework based on contrastive learning—the Predictive Biomarker Modeling Framework (PBMF)—that explores potential predictive biomarkers in an automated, systematic, and unbiased manner. Applied retrospectively to real clinicogenomic datasets, particularly for immuno-oncology (IO) trials, our algorithm identifies biomarkers of IO-treated individuals who survive longer than those treated with other therapies. We demonstrate how our framework retrospectively contributes to a phase 3 clinical trial by uncovering a predictive, interpretable biomarker based solely on early study data. Patients identified with this predictive biomarker show a 15% improvement in survival risk compared to those in the original trial. The PBMF offers a general-purpose, rapid, and robust approach to inform biomarker strategy, providing actionable outcomes for clinical decision-making.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"263 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841637","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