Cancer Cell最新文献_第8页

Integrated single cell analysis reveals co-evolution of malignant B cells and tumor micro-environment in transformed follicular lymphoma. 综合单细胞分析揭示了转化型滤泡淋巴瘤中恶性 B 细胞和肿瘤微环境的共同演化。

IF 48.8 1区医学

Cancer Cell Pub Date : 2024-09-09 Epub Date: 2024-08-15 DOI: 10.1016/j.ccell.2024.07.012

Clémentine Sarkozy, Shaocheng Wu, Katsuyoshi Takata, Tomohiro Aoki, Susana B Neriah, Katy Milne, Talia Goodyear, Celia Strong, Tashi Rastogi, Laura K Hilton, Daniel Lai, Laurie H Sehn, Pedro Farinha, Brad H Nelson, Andrew Weng, Marco Marra, David W Scott, Jeffrey W Craig, Christian Steidl, Andrew Roth

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Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma 单细胞的综合电生理和基因组图谱揭示了人类胶质瘤中的尖峰肿瘤细胞

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-09-05 DOI: 10.1016/j.ccell.2024.08.009

Rachel N. Curry, Qianqian Ma, Malcolm F. McDonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O. Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci

{"title":"Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma","authors":"Rachel N. Curry, Qianqian Ma, Malcolm F. McDonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O. Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci","doi":"10.1016/j.ccell.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.009","url":null,"abstract":"Prior studies have described the complex interplay that exists between glioma cells and neurons; however, the electrophysiological properties endogenous to glioma cells remain obscure. To address this, we employed Patch-sequencing (Patch-seq) on human glioma specimens and found that one-third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia. To define these hybrid cells (HCs), which fire single, short action potentials, and discern if they are of tumoral origin, we developed the single cell rule association mining (SCRAM) computational tool to annotate each cell individually. SCRAM revealed that HCs possess select features of GABAergic neurons and oligodendrocyte precursor cells, and include both tumor and non-tumor cells. These studies characterize the combined electrophysiological and molecular properties of human glioma cells and describe a cell type in human glioma with unique electrophysiological and transcriptomic properties that may also exist in the non-tumor brain.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"19 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142863","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

GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant GABA能神经元谱系的发展决定了弥漫性半球胶质瘤、H3G34突变体的临床作用靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-09-03 DOI: 10.1016/j.ccell.2024.08.006

Ilon Liu, Gustavo Alencastro Veiga Cruzeiro, Lynn Bjerke, Rebecca F. Rogers, Yura Grabovska, Alexander Beck, Alan Mackay, Tara Barron, Olivia A. Hack, Michael A. Quezada, Valeria Molinari, McKenzie L. Shaw, Marta Perez-Somarriba, Sara Temelso, Florence Raynaud, Ruth Ruddle, Eshini Panditharatna, Bernhard Englinger, Hafsa M. Mire, Li Jiang, Mariella G. Filbin

{"title":"GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant","authors":"Ilon Liu, Gustavo Alencastro Veiga Cruzeiro, Lynn Bjerke, Rebecca F. Rogers, Yura Grabovska, Alexander Beck, Alan Mackay, Tara Barron, Olivia A. Hack, Michael A. Quezada, Valeria Molinari, McKenzie L. Shaw, Marta Perez-Somarriba, Sara Temelso, Florence Raynaud, Ruth Ruddle, Eshini Panditharatna, Bernhard Englinger, Hafsa M. Mire, Li Jiang, Mariella G. Filbin","doi":"10.1016/j.ccell.2024.08.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.006","url":null,"abstract":"Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"3 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123931","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

Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy 用泊纳替尼和阿西米尼联合疗法克服临床BCR-ABL1复合突变耐药性

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.004

Christopher A. Eide, Diana Brewer, Tao Xie, Anna Reister Schultz, Samantha L. Savage, Serena Muratcioglu, Noah Merz, Richard D. Press, Thomas O’Hare, Thomas Jacob, Tania Q. Vu, Cristina E. Tognon, Tara A. Macey, John Kuriyan, Charalampos G. Kalodimos, Brian J. Druker

引用次数: 0

The KRAS mutational spectrum and its clinical implications in pancreatic cancer 胰腺癌 KRAS 基因突变谱及其临床意义

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.001

Luigi Perelli, Giannicola Genovese, Giulio F. Draetta

引用次数: 0

Precision oncology across the ages: Impact on children, adolescents, and young adults 跨年龄段的精准肿瘤学：对儿童、青少年和年轻人的影响

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.010

Vivek Subbiah, Razelle Kurzrock

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Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors 癌细胞状态：人类肿瘤单细胞 RNA 测序十年的启示

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.005

Itay Tirosh, Mario L. Suva

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PD-1 blockade is a promising therapeutic addition to neoadjuvant chemoradiation in locally advanced rectal cancer 在局部晚期直肠癌的新辅助化疗中，PD-1 阻断剂是一种很有前景的辅助疗法

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.003

Ashwin Somasundaram, Hanna K. Sanoff

引用次数: 0

Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer 人类胰腺癌中特定 KRAS 突变体的不同临床结果和生物学特征

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.002

Caitlin A. McIntyre, Adrien Grimont, Jiwoon Park, Yinuo Meng, Whitney J. Sisso, Kenneth Seier, Gun Ho Jang, Henry Walch, Victoria G. Aveson, David J. Falvo, William B. Fall, Christopher W. Chan, Andrew Wenger, Brett L. Ecker, Alessandra Pulvirenti, Rebecca Gelfer, Maria Paz Zafra, Nikolaus Schultz, Wungki Park, Eileen M. O’Reilly, Rohit Chandwani

{"title":"Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer","authors":"Caitlin A. McIntyre, Adrien Grimont, Jiwoon Park, Yinuo Meng, Whitney J. Sisso, Kenneth Seier, Gun Ho Jang, Henry Walch, Victoria G. Aveson, David J. Falvo, William B. Fall, Christopher W. Chan, Andrew Wenger, Brett L. Ecker, Alessandra Pulvirenti, Rebecca Gelfer, Maria Paz Zafra, Nikolaus Schultz, Wungki Park, Eileen M. O’Reilly, Rohit Chandwani","doi":"10.1016/j.ccell.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.002","url":null,"abstract":"KRAS mutations in pancreatic ductal adenocarcinoma (PDAC) are suggested to vary in oncogenicity but the implications for human patients have not been explored in depth. We examined 1,360 consecutive PDAC patients undergoing surgical resection and find that KRASG12R mutations are enriched in early-stage (stage I) disease, owing not to smaller tumor size but increased node-negativity. KRASG12R tumors are associated with decreased distant recurrence and improved survival as compared to KRASG12D. To understand the biological underpinnings, we performed spatial profiling of 20 patients and bulk RNA-sequencing of 100 tumors, finding enhanced oncogenic signaling and epithelial-mesenchymal transition (EMT) in KRASG12D and increased nuclear factor κB (NF-κB) signaling in KRASG12R tumors. Orthogonal studies of mouse KrasG12R PDAC organoids show decreased migration and improved survival in orthotopic models. KRAS alterations in PDAC are thus associated with distinct presentation, clinical outcomes, and biological behavior, highlighting the prognostic value of mutational analysis and the importance of articulating mutation-specific PDAC biology.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"57 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090447","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

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells 抗-PD-1和抗-CTLA-4疗法联合疗法产生的克隆反应波包括祖细胞耗竭的CD8+T细胞

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-08-29 DOI: 10.1016/j.ccell.2024.08.007

Kevin Wang, Paulina Coutifaris, David Brocks, Guanning Wang, Tarek Azar, Sabrina Solis, Ajeya Nandi, Shaneaka Anderson, Nicholas Han, Sasikanth Manne, Evgeny Kiner, Chirag Sachar, Minke Lucas, Sangeeth George, Patrick K. Yan, Melanie W. Kier, Amy I. Laughlin, Shawn Kothari, Josephine Giles, Divij Mathew, Alexander C. Huang

{"title":"Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells","authors":"Kevin Wang, Paulina Coutifaris, David Brocks, Guanning Wang, Tarek Azar, Sabrina Solis, Ajeya Nandi, Shaneaka Anderson, Nicholas Han, Sasikanth Manne, Evgeny Kiner, Chirag Sachar, Minke Lucas, Sangeeth George, Patrick K. Yan, Melanie W. Kier, Amy I. Laughlin, Shawn Kothari, Josephine Giles, Divij Mathew, Alexander C. Huang","doi":"10.1016/j.ccell.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.08.007","url":null,"abstract":"Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. Here, we perform paired single-cell RNA and T cell receptor (TCR) sequencing across time in 36 patients with stage IV melanoma treated with anti-PD-1, anti-CTLA-4, or combination therapy. We develop the algorithm Cyclone to track temporal clonal dynamics and underlying cell states. Checkpoint blockade induces waves of clonal T cell responses that peak at distinct time points. Combination therapy results in greater magnitude of clonal responses at 6 and 9 weeks compared to single-agent therapies, including melanoma-specific CD8+ T cells and exhausted CD8+ T cell (TEX) clones. Focused analyses of TEX identify that anti-CTLA-4 induces robust expansion and proliferation of progenitor TEX, which synergizes with anti-PD-1 to reinvigorate TEX during combination therapy. These next generation immune profiling approaches can guide the selection of drugs, schedule, and dosing for novel combination strategies.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"379 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090513","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