Cancer CellPub Date : 2025-03-10DOI: 10.1016/j.ccell.2025.02.016
Ting Liu, Leif W. Ellisen
{"title":"Exploring the “chemo” in chemoimmunotherapy for triple-negative breast cancer","authors":"Ting Liu, Leif W. Ellisen","doi":"10.1016/j.ccell.2025.02.016","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.016","url":null,"abstract":"In this issue of <em>Cancer Cell</em>, Zhang et al. use single-cell RNA sequencing to compare immune cell dynamics in triple-negative breast cancers treated with the PD-L1 inhibitor atezolizumab plus paclitaxel or nab-paclitaxel. They identify distinct T cell activation patterns and highlight mast cells’ role in immune activation exclusively in the nab-paclitaxel combination.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"19 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582432","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":"Single-cell multi-stage spatial evolutional map of esophageal carcinogenesis","authors":"Jiang Chang, Junting Lu, Qingyi Liu, Tao Xiang, Shaosen Zhang, Yonglin Yi, Dongxu Li, Tianyuan Liu, Zeyuan Liu, Xinjie Chen, Zhenghao Dong, Cainan Li, HanZhang Yi, Siqi Yu, Luwei Huang, Fangfei Qu, Mengdi Wang, Dehe Wang, Hao Dong, Guoyu Cheng, Chen Wu","doi":"10.1016/j.ccell.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.009","url":null,"abstract":"Cancer development involves the co-evolution of cancer cells and their surrounding microenvironment, yet the dynamics of this interaction within the physical architecture remains poorly understood. Here, we present a spatial transcriptomic map at single-cell resolution, encompassing 127 multi-stage fields of view from 43 patients, to chart the evolutionary trajectories of human esophageal squamous cell carcinoma (ESCC). By analyzing 6.4 million cells, we reveal that ESCC progression is driven by a proliferative epithelial cell subpopulation that acquires dedifferentiated and invasive characteristics. At the late precancerous stage, these cells disrupt the epithelial-stromal interface and recruit normal fibroblasts via JAG1-NOTCH1 signaling, transforming them into cancer-associated fibroblasts (CAFs). This interaction leads to the formation of a “CAF-Epi” (CAF and epithelial cell) niche at the tumor edge that shields the tumor from immune surveillance. The CAF-Epi niche formation is a key indicator of progression in ESCC and other squamous cell carcinomas and patient outcomes.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"62 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582533","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 : 2025-03-06DOI: 10.1016/j.ccell.2025.02.002
W.K. Jacky Lam, Guannan Kang, Charles M.L. Chan, Vicky C.T. Lee, Mary-Jane L. Ma, Qing Zhou, Peiyong Jiang, Irene O.L. Tse, Ann D. King, Kenneth C.W. Wong, Edwin P. Hui, Brigette B.Y. Ma, Anthony T.C. Chan, K.C. Allen Chan, Y.M. Dennis Lo
{"title":"Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma","authors":"W.K. Jacky Lam, Guannan Kang, Charles M.L. Chan, Vicky C.T. Lee, Mary-Jane L. Ma, Qing Zhou, Peiyong Jiang, Irene O.L. Tse, Ann D. King, Kenneth C.W. Wong, Edwin P. Hui, Brigette B.Y. Ma, Anthony T.C. Chan, K.C. Allen Chan, Y.M. Dennis Lo","doi":"10.1016/j.ccell.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.002","url":null,"abstract":"Fragmentomics analysis of plasma autosomal DNA has shown promise in cancer diagnostics. Here we evaluated the clinical utility of plasma Epstein-Barr virus (EBV) DNA fragmentomics analysis for nasopharyngeal carcinoma (NPC) screening. Among our prospective cohort of approximately 20,000 subjects that underwent two rounds of screening, we analyzed the first-round blood samples of subjects who tested positive for EBV DNA via polymerase chain reaction (PCR) (<em>n</em> = 558). We found that those who subsequently developed NPC in the second round exhibited a distinctive mononucleosomal size pattern, an NPC-associated end motif (specifically, a depletion of CC-motif) and aberrations in methylation identified through fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher quantity of EBV DNA had a relative risk of 87.1 times greater for developing NPC in the second round compared to subjects tested negative for EBV DNA on PCR. These results demonstrate plasma DNA fragmentomics could predict future cancer risk.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"26 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569571","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 : 2025-03-06DOI: 10.1016/j.ccell.2025.02.025
Lindsay M. LaFave, Vinay K. Kartha, Sai Ma, Kevin Meli, Isabella Del Priore, Caleb Lareau, Santiago Naranjo, Peter M.K. Westcott, Fabiana M. Duarte, Venkat Sankar, Zachary Chiang, Alison Brack, Travis Law, Haley Hauck, Annalisa Okimoto, Aviv Regev, Jason D. Buenrostro, Tyler Jacks
{"title":"Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma","authors":"Lindsay M. LaFave, Vinay K. Kartha, Sai Ma, Kevin Meli, Isabella Del Priore, Caleb Lareau, Santiago Naranjo, Peter M.K. Westcott, Fabiana M. Duarte, Venkat Sankar, Zachary Chiang, Alison Brack, Travis Law, Haley Hauck, Annalisa Okimoto, Aviv Regev, Jason D. Buenrostro, Tyler Jacks","doi":"10.1016/j.ccell.2025.02.025","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.025","url":null,"abstract":"(Cancer Cell <em>38</em>, 212–228; August 10, 2020)","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"14 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569569","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 : 2025-03-06DOI: 10.1016/j.ccell.2025.02.017
Sara Lamorte, Rene Quevedo, Robbie Jin, Luke Neufeld, Zhe Qi Liu, M. Teresa Ciudad, Sabelo Lukhele, Jessica Bruce, Shreya Mishra, Xin Zhang, Zaid Kamil Saeed, Hal Berman, Dana J. Philpott, Stephen E. Girardin, Shane Harding, David H. Munn, Tak W. Mak, Mikael C.I. Karlsson, David G. Brooks, Tracy L. McGaha
{"title":"Lymph node macrophages drive immune tolerance and resistance to cancer therapy by induction of the immune-regulatory cytokine IL-33","authors":"Sara Lamorte, Rene Quevedo, Robbie Jin, Luke Neufeld, Zhe Qi Liu, M. Teresa Ciudad, Sabelo Lukhele, Jessica Bruce, Shreya Mishra, Xin Zhang, Zaid Kamil Saeed, Hal Berman, Dana J. Philpott, Stephen E. Girardin, Shane Harding, David H. Munn, Tak W. Mak, Mikael C.I. Karlsson, David G. Brooks, Tracy L. McGaha","doi":"10.1016/j.ccell.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.017","url":null,"abstract":"Apoptotic cells are immunosuppressive, creating a barrier in cancer treatment. Thus, we investigated immune responses to dying tumor cells after therapy in the tumor draining lymph node (TDLN). A key population responsible for clearing tumor material in the TDLN was medullary sinus macrophages (MSMs). Tumor debris phagocytosis by MSMs induces the cytokine IL-33, and blocking the IL-33 receptor (ST2) or deletion of <em>Il33</em> in MSMs enhances therapy responses. Mechanistically, IL-33 activates T regulatory cells in TDLNs that migrate to the tumor to suppress CD8<sup>+</sup> T cells. Therapeutically combining ST2 blockade, targeted kinase inhibitors, and anti-PD-1 immunotherapy increases CD8<sup>+</sup> T cell activity promoting tumor regression. Importantly, we observe similar activity in human macrophages, and IL-33 expression in sentinel lymph nodes correlates with disease stage and survival in melanoma. Thus, our data identifies an IL-33-dependent immune response to therapy that attenuates therapy-induced anti-tumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"85 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569568","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":"Hypoxia inducible factor-1α drives cancer resistance to cuproptosis","authors":"Zhou Yang, Wei Su, Xiyi Wei, Yitong Pan, Mengying Xing, Lili Niu, Baijie Feng, Weiyu Kong, Xiaohan Ren, Feng Huang, Jingwan Zhou, Wei Zhao, Yingyi Qiu, Tian Liao, Qi Chen, Shuang Qu, Yunjun Wang, Qing Guan, Duanshu Li, Ke Zen, Bing Yao","doi":"10.1016/j.ccell.2025.02.015","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.015","url":null,"abstract":"Cuproptosis represents a new type of cell death that intricately associated with copper homeostasis and protein lipoylation. The cuproptosis suppression has been characterized in the hypoxic tumor microenvironment (TME). Here we reveal that hypoxia inducible factor-1α (HIF-1α) is a driver of cuproptosis resistance in solid tumor. We found that HIF-1α activates pyruvate dehydrogenase kinase 1 and 3 (PDK1/3), resulting in decreased expression of dihydrolipoamide S-acetyltransferase (DLAT) (target of copper), and promotes the accumulation of metallothionein, which sequesters mitochondrial copper, leading to resistance to cuproptosis under hypoxic conditions. Furthermore, we discovered that high levels of copper reduce ubiquitination and increase the stability of HIF-1α protein without affecting its mRNA levels. Inhibition of HIF-1α increases the susceptibility of cancer to cuproptosis <em>in vivo</em>. This study unveils the multifaceted role of HIF-1α in cuproptosis and demonstrates the molecular mechanism of hypoxia-promoted carcinogenesis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"17 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569570","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":"Nivolumab combined with induction chemotherapy and radiotherapy in nasopharyngeal carcinoma: A multicenter phase 2 PLATINUM trial","authors":"Cheng Xu, Guan-Qun Zhou, Wen-Fei Li, De-Sheng Hu, Xiao-Zhong Chen, Shao-Jun Lin, Feng Jin, Xin-Qiong Huang, Gang Peng, Jing Huang, Yuan Wu, Chang-Juan Tao, Ji-Bin Li, Ai-Hua Lin, Hong-Yun Zhao, Shu-Bin Hong, Hui-Ling Huang, Ling-Long Tang, Ying-Lin Peng, Ke-Fu Shi, Jun Ma","doi":"10.1016/j.ccell.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.01.014","url":null,"abstract":"Severe toxicities caused by concurrent cisplatin are a critical problem in nasopharyngeal carcinoma (NPC) treatment. In this phase 2 multicenter PLATINUM trial (<span><span>NCT03984357</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>), we recruited 152 NPC patients who received 12-cycle nivolumab plus induction chemotherapy and radiotherapy without concurrent cisplatin. After a median follow-up of 43 months, the 3-year failure-free survival (FFS) was 88.5% (95% confidence interval [CI], 83.4%–93.8%) and the 3-year overall survival was 97.9%. An early clearance of Epstein-Barr virus (EBV) DNA after induction-phase treatment was associated with FFS benefit. Sixty (40.2%) and eight (5.2%) patients had acute and late grade 3–4 adverse events (AEs), respectively. Most patients had good tolerance to AE-associated frequency (68.0%–96.7%), severity (56.0%–98.6%), and interference (58.0%–98.0%); 86.7%–100.0% of quality-of-life domains showed either no clinically meaningful deterioration or a rapid recovery. Nivolumab plus induction chemotherapy and radiotherapy demonstrated efficacious anti-tumor activity, low toxicity, and favorable tolerability and quality-of-life for NPC patients.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"2 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506858","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 : 2025-02-27DOI: 10.1016/j.ccell.2025.02.003
Susanne Müller, Domenico Sanfelice, Paul Workman
{"title":"Probing cancer with small-molecule tools—Progress and challenges","authors":"Susanne Müller, Domenico Sanfelice, Paul Workman","doi":"10.1016/j.ccell.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.003","url":null,"abstract":"Chemical probes are powerful small-molecule tools in fundamental and translational cancer research. They are highly versatile, complementing genetic technologies in the annotation of protein function, and invaluable in target validation and drug discovery. However, continued improvements are needed to enhance best practices in selection and use of chemical probes. We discuss progress over the last decade, highlight key issues, and indicate a path to generate a high-quality chemical probe for every human protein.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"32 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506860","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":"Global alliances in translational cancer research","authors":"Hui-Yan Luo, Yun-Xin Lu, Kohei Shitara, Heinz-Josef Lenz, Rui-Hua Xu","doi":"10.1016/j.ccell.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.005","url":null,"abstract":"Translating basic cancer biology into effective clinical therapies remains a major challenge due to differences in research models, communication gaps, and limited funding. This commentary underscores the transformative potential of international collaborations, which integrate diverse resources, multidisciplinary talents, and innovative trial designs to bridge the gap between laboratory discoveries and clinical applications. By fostering global alliances, sharing knowledge, and harmonizing regulatory and funding frameworks, we can accelerate breakthroughs in cancer treatment, improving patient outcomes worldwide.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"27 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506855","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 : 2025-02-27DOI: 10.1016/j.ccell.2025.02.004
Tanya Schild, Patrick Wallisch, Yixuan Zhao, Ya-Ting Wang, Lyric Haughton, Rachel Chirayil, Kaitlyn Pierpont, Kevin Chen, Sara Nunes-Violante, Justin Cross, Elisa de Stanchina, Craig B. Thompson, David A. Scheinberg, Justin S.A. Perry, Kayvan R. Keshari
{"title":"Metabolic engineering to facilitate anti-tumor immunity","authors":"Tanya Schild, Patrick Wallisch, Yixuan Zhao, Ya-Ting Wang, Lyric Haughton, Rachel Chirayil, Kaitlyn Pierpont, Kevin Chen, Sara Nunes-Violante, Justin Cross, Elisa de Stanchina, Craig B. Thompson, David A. Scheinberg, Justin S.A. Perry, Kayvan R. Keshari","doi":"10.1016/j.ccell.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.02.004","url":null,"abstract":"Fructose consumption is elevated in western diets, but its impact on anti-tumor immunity is unclear. Fructose is metabolized in the liver and small intestine, where fructose transporters are highly expressed. Most tumors are unable to drive glycolytic flux using fructose, enriching fructose in the tumor microenvironment (TME). Excess fructose in the TME may be utilized by immune cells to enhance effector functions if engineered to express the fructose-specific transporter GLUT5. Here, we show that GLUT5-expressing CD8<sup>+</sup> T cells, macrophages, and chimeric antigen receptor (CAR) T cells all demonstrate improved effector functions in glucose-limited conditions <em>in vitro</em>. GLUT5-expressing T cells show high fructolytic activity <em>in vitro and</em> higher anti-tumor efficacy in murine syngeneic and human xenograft models <em>in vivo</em>, especially following fructose supplementation. Together, our data demonstrates that metabolic engineering through GLUT5 enables immune cells to efficiently utilize fructose and boosts anti-tumor immunity in the glucose-limited TME.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"66 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506857","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
