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Learning the language of T cell receptors through large-scale screening 通过大规模筛选学习 T 细胞受体的语言
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.032
Živa Moravec, John B.A.G. Haanen, Ton N. Schumacher, Wouter Scheper
{"title":"Learning the language of T cell receptors through large-scale screening","authors":"Živa Moravec, John B.A.G. Haanen, Ton N. Schumacher, Wouter Scheper","doi":"10.1016/j.ccell.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.032","url":null,"abstract":"T cells perform critical roles in orchestrating immunity in health and disease. However, decoding what individual T cells recognize has long been challenging due to the immense diversity of both T cell receptors (TCRs) and potential antigens. Recent advances in high-throughput TCR screening approaches now provide an opportunity to map the antigen specificity landscape of T cells with unprecedented depth. Here, we outline these recent developments in screening methodologies and discuss how these can help advance our fundamental understanding of T cell-based immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"37 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841638","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
Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation 环状RMST与谱系驱动转录因子共同调控神经内分泌转分化
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.027
Mona Teng, Jiacheng Guo, Xin Xu, Xinpei Ci, Yulin Mo, Yakup Kohen, Zuyao Ni, Sujun Chen, Wang Yuan Guo, Martin Bakht, Shengyu Ku, Michael Sigouros, Wenqin Luo, Colette Maya Macarios, Ziting Xia, Moliang Chen, Sami Ul Haq, Wen Yang, Alejandro Berlin, Theo van der Kwast, Housheng Hansen He
{"title":"Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation","authors":"Mona Teng, Jiacheng Guo, Xin Xu, Xinpei Ci, Yulin Mo, Yakup Kohen, Zuyao Ni, Sujun Chen, Wang Yuan Guo, Martin Bakht, Shengyu Ku, Michael Sigouros, Wenqin Luo, Colette Maya Macarios, Ziting Xia, Moliang Chen, Sami Ul Haq, Wen Yang, Alejandro Berlin, Theo van der Kwast, Housheng Hansen He","doi":"10.1016/j.ccell.2025.03.027","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.027","url":null,"abstract":"Circular RNA (circRNA) is a class of noncoding RNA with regulatory potentials. Its role in the transdifferentiation of prostate and lung adenocarcinoma into neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC) remains unexplored. Here, we identified <em>circRMST</em> as an exceptionally abundant circRNA predominantly expressed in NEPC and SCLC, with strong conservation between humans and mice. Functional studies using shRNA, siRNA, CRISPR-Cas13, and Cas9 consistently demonstrate that <em>circRMST</em> is essential for tumor growth and the expression of ASCL1, a master regulator of neuroendocrine fate. Genetic knockout of <em>Rmst</em> in NEPC genetic engineered mouse models prevents neuroendocrine transdifferentiation, maintaining tumors in an adenocarcinoma state. Mechanistically, <em>circRMST</em> physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of <em>circRMST</em> induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of <em>ASCL1</em> transcription.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"18 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841635","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
Complexity of insulin resistance in early-onset colorectal cancer 早发性结直肠癌胰岛素抵抗的复杂性
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.033
Samson Mathews Samuel, Elizabeth Varghese, Dietrich Büsselberg
{"title":"Complexity of insulin resistance in early-onset colorectal cancer","authors":"Samson Mathews Samuel, Elizabeth Varghese, Dietrich Büsselberg","doi":"10.1016/j.ccell.2025.03.033","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.033","url":null,"abstract":"Early-life exposure to lifestyle-associated metabolic alterations could be a key contributor to early-onset colorectal cancer (EOCRC). Notably, insulin resistance (InsR)-linked hyperinsulinemia, elevated levels of insulin-like growth factors, and chronic inflammation could trigger EOCRC by modulating gene expression/pathways that support carcinogenesis/anti-apoptosis. Here, we discuss how InsR could be the trigger that offsets metabolic homeostasis in young individuals, leading to EOCRC. Furthermore, we emphasize the need for lifestyle interventions, early detection, and targeted therapeutic interventions to mitigate this growing health concern.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"30 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841634","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
Cell death, IL-1 cytokines, and tumor progression 细胞死亡、IL-1细胞因子与肿瘤进展
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.030
Long Cheng, Ying Zhang
{"title":"Cell death, IL-1 cytokines, and tumor progression","authors":"Long Cheng, Ying Zhang","doi":"10.1016/j.ccell.2025.03.030","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.030","url":null,"abstract":"Tumor cell death shapes tumorigenesis and antitumor immunity in complex ways. Recently, Hänggi et al. revealed that necrotic-like death releases interleukin-1α (IL-1α), driving myeloid-mediated immunosuppression. Lamorte et al. demonstrated that medullary sinus macrophage (MSM) efferocytosis of apoptotic tumor cells activates the IL-33-regulatory T cell (Treg) axis, accelerating tumor growth. Blocking these pathways enhances the efficacy of cancer immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"74 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841636","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 circular RNA in neuroendocrine carcinomas 神经内分泌癌中的环状RNA
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-17 DOI: 10.1016/j.ccell.2025.03.028
Yixiang Li, Matthew G. Oser
{"title":"A circular RNA in neuroendocrine carcinomas","authors":"Yixiang Li, Matthew G. Oser","doi":"10.1016/j.ccell.2025.03.028","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.028","url":null,"abstract":"In this issue of <em>Cancer Cell</em>, Teng et al. discover that small cell lung cancer and neuroendocrine prostate cancer highly express a circular RNA known as <em>circRMST.</em> They show that <em>circRMST</em> is necessary for these neuroendocrine cancers to promote their ASCL1-positive neuroendocrine phenotype through binding lineage transcription factors that promote ASCL1 expression.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"4 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841639","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
Precision oncology and genetic ancestry: The science behind population-based cancer disparities 精确肿瘤学和遗传祖先：基于人群的癌症差异背后的科学
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.022
Melissa Boneta Davis, Rachel Martini
{"title":"Precision oncology and genetic ancestry: The science behind population-based cancer disparities","authors":"Melissa Boneta Davis, Rachel Martini","doi":"10.1016/j.ccell.2025.03.022","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.022","url":null,"abstract":"Precision oncology has transformed cancer care but has barely benefited patients of diverse ancestry. Historically, self-reported race/ethnicity has served as a surrogate for biological differences, but genetic ancestry provides a more precise framework for understanding genetic drivers of cancer disparities, including associations between ancestry and tumor subtypes, and genetic variants affecting drug metabolism and treatment response. To improve precision oncology for all patients and reduce cancer disparities, we propose expanding ancestry-inclusive genomic data, reevaluating disease-associated variants within ancestrally diverse cohorts, and standardizing data-sharing practices.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"16 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827150","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
Many paths, one destination: Bridging the gap in cancer care 许多途径，一个目标：弥合癌症治疗的差距
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.026
Erik Sahai, Hongxia Wang, Marleen Kok, Catherine J. Wu, Lin Shen, John Carpten, César Serrano, Varun Venkataramani
{"title":"Many paths, one destination: Bridging the gap in cancer care","authors":"Erik Sahai, Hongxia Wang, Marleen Kok, Catherine J. Wu, Lin Shen, John Carpten, César Serrano, Varun Venkataramani","doi":"10.1016/j.ccell.2025.03.026","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.026","url":null,"abstract":"This special issue of <em>Cancer Cell</em> is dedicated to “bridging the gap between foundational cancer biology and clinical oncology.” We asked scientists and clinicians to give us a brief “state of the field,” discussing the integration of new technologies, the importance of patient-centric approaches, the need for innovative clinical trial designs, and how fostering teamwork and inclusive research can help us bridge the gap between cancer research and effective clinical applications.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"137 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827382","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
New horizons at the interface of artificial intelligence and translational cancer research 人工智能与转化性癌症研究的新视野
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.018
Josephine Yates, Eliezer M. Van Allen
{"title":"New horizons at the interface of artificial intelligence and translational cancer research","authors":"Josephine Yates, Eliezer M. Van Allen","doi":"10.1016/j.ccell.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.018","url":null,"abstract":"Artificial intelligence (AI) is increasingly being utilized in cancer research as a computational strategy for analyzing multiomics datasets. Advances in single-cell and spatial profiling technologies have contributed significantly to our understanding of tumor biology, and AI methodologies are now being applied to accelerate translational efforts, including target discovery, biomarker identification, patient stratification, and therapeutic response prediction. Despite these advancements, the integration of AI into clinical workflows remains limited, presenting both challenges and opportunities. This review discusses AI applications in multiomics analysis and translational oncology, emphasizing their role in advancing biological discoveries and informing clinical decision-making. Key areas of focus include cellular heterogeneity, tumor microenvironment interactions, and AI-aided diagnostics. Challenges such as reproducibility, interpretability of AI models, and clinical integration are explored, with attention to strategies for addressing these hurdles. Together, these developments underscore the potential of AI and multiomics to enhance precision oncology and contribute to advancements in cancer care.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"25 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827141","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
Bridging the gap: The future of cancer research and clinical oncology in Cancer Cell 弥合差距：癌症研究和临床肿瘤学的未来
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.024
Steve Mao
{"title":"Bridging the gap: The future of cancer research and clinical oncology in Cancer Cell","authors":"Steve Mao","doi":"10.1016/j.ccell.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.024","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Over the past five years, <em>Cancer Cell</em> has undergone a transformative evolution, reflecting the increasing multidisciplinary and integrative nature of cancer research. As editor-in-chief, it has been both a privilege and a profound responsibility to guide this journal through a period of significant change and growth, ensuring that it remains at the forefront of cancer research while adapting to the evolving needs of the scientific community. None of this would have been possible without the</section></section>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"26 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827138","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
CAR-T therapy in solid tumors CAR-T疗法在实体瘤中的应用
IF 50.3 1区 医学
Cancer Cell Pub Date : 2025-04-14 DOI: 10.1016/j.ccell.2025.03.019
Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu
{"title":"CAR-T therapy in solid tumors","authors":"Bing Du, Juliang Qin, Boxu Lin, Jiqin Zhang, Dali Li, Mingyao Liu","doi":"10.1016/j.ccell.2025.03.019","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.03.019","url":null,"abstract":"While chimeric antigen receptor (CAR) T cell therapy has shown great success in hematologic malignancies, the effectiveness in solid tumors has been limited by several factors, including antigenic heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). In this review, we discuss the advancements made in clinical studies and challenges faced by CAR-T therapy for solid tumors. To enhance CAR-T cell efficacy in solid tumors, we explore strategies such as enhancing T cell persistence and cytotoxicity, targeting multiple antigens, and utilizing innovative allogeneic CAR-T cell manufacturing. Additionally, we highlight the potential benefits of combining CAR-T therapies with immune checkpoint inhibitors and other treatment modalities to overcome TME limitations. We remain optimistic about the future of CAR-T cell therapy in solid tumors, emphasizing the need for continued research to refine therapeutic approaches and address the clinical needs of patients with cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"31 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827140","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
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