Cancer Cell最新文献_第3页

Itaconate promotes an unexpected tumor immune escape mechanism 伊塔康酸促进一种意想不到的肿瘤免疫逃逸机制

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-11-14 DOI: 10.1016/j.ccell.2024.10.011

Lara Haase, Christian Frezza

引用次数: 0

In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy 造血恶性肿瘤亚克隆肿瘤发生和依赖性的体内模型

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-11-11 DOI: 10.1016/j.ccell.2024.10.009

Robert L. Bowman, Andrew J. Dunbar, Tanmay Mishra, Wenbin Xiao, Michael R. Waarts, Inés Fernández Maestre, Shira E. Eisman, Louise Cai, Shoron Mowla, Nisargbhai Shah, Angela Youn, Laura Bennett, Suean Fontenard, Shreeya Gounder, Anushka Gandhi, Michael Bowman, Kavi O’Connor, Zachary Zaroogian, Pablo Sánchez-Vela, Anthony R. Martinez Benitez, Ross L. Levine

{"title":"In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy","authors":"Robert L. Bowman, Andrew J. Dunbar, Tanmay Mishra, Wenbin Xiao, Michael R. Waarts, Inés Fernández Maestre, Shira E. Eisman, Louise Cai, Shoron Mowla, Nisargbhai Shah, Angela Youn, Laura Bennett, Suean Fontenard, Shreeya Gounder, Anushka Gandhi, Michael Bowman, Kavi O’Connor, Zachary Zaroogian, Pablo Sánchez-Vela, Anthony R. Martinez Benitez, Ross L. Levine","doi":"10.1016/j.ccell.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.10.009","url":null,"abstract":"Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes. Here, we integrate multi-recombinase tools for reversible, sequential mutagenesis from premalignancy to leukemia. We demonstrate that inducible Flt3 mutations differentially cooperate with Dnmt3a, Idh2, and Npm1 mutant alleles, and that changing the order of mutations influences cellular and transcriptional landscapes. We next use a generalizable, reversible approach to demonstrate that mutation reversion results in rapid leukemic regression with distinct differentiation patterns depending upon co-occurring mutations. These studies provide a path to experimentally model sequential mutagenesis, investigate mechanisms of transformation and probe oncogenic dependency in disease evolution.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"41 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599558","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

Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion 由 TP53 介导的雌激素转化确定乳腺癌对 CDK4/6 抑制的长期反应

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-11-11 DOI: 10.1016/j.ccell.2024.10.013

Rei Kudo, Anton Safonov, Catherine Jones, Enrico Moiso, Jonathan R. Dry, Hong Shao, Sharanya Nag, Edaise M. da Silva, Selma Yeni Yildirim, Qing Li, Elizabeth O’Connell, Payal Patel, Marie Will, Atsushi Fushimi, Marimar Benitez, Martina Bradic, Li Fan, Harikrishna Nakshatri, Dhivya R. Sudhan, Christopher R. Denz, Sarat Chandarlapaty

引用次数: 0

Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy 针对肿瘤启动细胞的免疫特权，加强癌症免疫疗法

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-11-07 DOI: 10.1016/j.ccell.2024.10.008

Chen Yang, Haigang Geng, Xupeng Yang, Shuyi Ji, Zhicheng Liu, Hao Feng, Qian Li, Tangansu Zhang, Sisi Zhang, Xuhui Ma, Chuchen Zhu, Nuo Xu, Yuhan Xia, Yan Li, Hongye Wang, Chune Yu, Shangce Du, Beiping Miao, Lei Xu, Hui Wang, Cun Wang

{"title":"Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy","authors":"Chen Yang, Haigang Geng, Xupeng Yang, Shuyi Ji, Zhicheng Liu, Hao Feng, Qian Li, Tangansu Zhang, Sisi Zhang, Xuhui Ma, Chuchen Zhu, Nuo Xu, Yuhan Xia, Yan Li, Hongye Wang, Chune Yu, Shangce Du, Beiping Miao, Lei Xu, Hui Wang, Cun Wang","doi":"10.1016/j.ccell.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.10.008","url":null,"abstract":"Tumor-initiating cells (TICs) possess the ability to evade anti-tumor immunity, potentially explaining many failures of cancer immunotherapy. Here, we identify CD49f as a prominent marker for discerning TICs in hepatocellular carcinoma (HCC), outperforming other commonly used TIC markers. CD49f-high TICs specifically recruit tumor-promoting neutrophils via the CXCL2-CXCR2 axis and create an immunosuppressive milieu in the tumor microenvironment (TME). Reciprocally, the neutrophils reprogram nearby tumor cells toward a TIC phenotype via secreting CCL4. These cells can evade CD8+ T cell-mediated killing through CCL4/STAT3-induced and CD49f-stabilized CD155 expression. Notably, while aberrant CD155 expression contributes to immune suppression, it also represents a TIC-specific vulnerability. We demonstrate that either CD155 deletion or antibody blockade significantly enhances sensitivity to anti-PD-1 therapy in preclinical HCC models. Our findings reveal a new mechanism of tumor immune evasion and provide a rationale for combining CD155 blockade with anti-PD-1/PD-L1 therapy in HCC.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"92 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594595","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

Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance 衣康酸转运体 SLC13A3 通过赋予铁变态反应抗性损害肿瘤免疫力

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-11-07 DOI: 10.1016/j.ccell.2024.10.010

Heng Lin, Kole Tison, Yuheng Du, Paul Kirchhoff, Chan Kim, Weichao Wang, Hannah Yang, Michael Pitter, Jiali Yu, Peng Liao, Jiajia Zhou, Linda Vatan, Sara Grove, Shuang Wei, Thomas Vigil, Yatrik M. Shah, Richard Mortensen, Ilona Kryczek, Lana Garmire, Jwala P. Sivaccumar, Weiping Zou

{"title":"Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance","authors":"Heng Lin, Kole Tison, Yuheng Du, Paul Kirchhoff, Chan Kim, Weichao Wang, Hannah Yang, Michael Pitter, Jiali Yu, Peng Liao, Jiajia Zhou, Linda Vatan, Sara Grove, Shuang Wei, Thomas Vigil, Yatrik M. Shah, Richard Mortensen, Ilona Kryczek, Lana Garmire, Jwala P. Sivaccumar, Weiping Zou","doi":"10.1016/j.ccell.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.10.010","url":null,"abstract":"Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME). Here, we discover SLC13A3 is an itaconate transporter in tumor cells and endows tumor ferroptosis resistance, diminishing tumor immunity and ICB efficacy. Mechanistically, tumor cells uptake itaconate via SLC13A3 from tumor-associated macrophages (TAMs), thereby activating the NRF2-SLC7A11 pathway and escaping from immune-mediated ferroptosis. Structural modeling and molecular docking analysis identify a functional inhibitor for SLC13A3 (SLC13A3i). Deletion of ACOD1 (an essential enzyme for itaconate synthesis) in macrophages, genetic ablation of SLC13A3 in tumors, or treatment with SLC13A3i sensitize tumors to ferroptosis, curb tumor progression, and bolster ICB effectiveness. Thus, we identify the interplay between tumors and TAMs via the SLC13A3-itaconate-NRF2-SLC7A11 axis as a previously unknown immune ferroptosis resistant mechanism in the TME and SLC13A3 as a promising immunometabolic target for treating SLC13A3+ cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"18 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594594","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

Intratumoral vidutolimod in combination with PD-1 blockade in locoregionally advanced melanoma 瘤体内维杜莫德联合 PD-1 阻断治疗局部晚期黑色素瘤

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-31 DOI: 10.1016/j.ccell.2024.10.001

James W. Smithy, Michael A. Postow

引用次数: 0

Targeting DLK1 in neuroblastoma 以神经母细胞瘤中的 DLK1 为靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-31 DOI: 10.1016/j.ccell.2024.10.006

引用次数: 0

Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial 新辅助维杜莫德和 nivolumab 治疗高风险可切除黑色素瘤：前瞻性 II 期试验

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-31 DOI: 10.1016/j.ccell.2024.10.007

Diwakar Davar, Robert M. Morrison, Amiran K. Dzutsev, Arivarasan Karunamurthy, Joe-Marc Chauvin, Florent Amatore, Julie S. Deutsch, Rodrigo X. Das Neves, Richard R. Rodrigues, John A. McCulloch, Hong Wang, Douglas J. Hartman, Jonathan H. Badger, Miriam R. Fernandes, Yulong Bai, Jie Sun, Alicia M. Cole, Poonam Aggarwal, Jennifer R. Fang, Christopher Deitrick, Hassane M. Zarour

{"title":"Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial","authors":"Diwakar Davar, Robert M. Morrison, Amiran K. Dzutsev, Arivarasan Karunamurthy, Joe-Marc Chauvin, Florent Amatore, Julie S. Deutsch, Rodrigo X. Das Neves, Richard R. Rodrigues, John A. McCulloch, Hong Wang, Douglas J. Hartman, Jonathan H. Badger, Miriam R. Fernandes, Yulong Bai, Jie Sun, Alicia M. Cole, Poonam Aggarwal, Jennifer R. Fang, Christopher Deitrick, Hassane M. Zarour","doi":"10.1016/j.ccell.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.10.007","url":null,"abstract":"Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67+CD8+ T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. MPRs gut microbiota were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov<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> identifier: NCT03618641<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>.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"213 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556313","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

Fertility outcomes post immune checkpoint inhibitor exposure 接触免疫检查点抑制剂后的生育结果

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-31 DOI: 10.1016/j.ccell.2024.10.005

Emily C. Harrold, Martinique Ogle, Erin O’Brien, Callahan Wilde, Jenna Sinopoli, Jill Weiss, Lauren Martino, Anne Casson, Hey-Joo Kang, Michael Postow, Andrea Cercek

引用次数: 0

Finding the right friends: Stromal composition influences TLS formation in ovarian cancer 寻找合适的朋友基质成分影响卵巢癌中TLS的形成

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-31 DOI: 10.1016/j.ccell.2024.10.004

Lloyd Bod

引用次数: 0