Cancer Cell最新文献_第2页

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<sup>+</sup> 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<sup>+</sup> tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67<sup>+</sup>CD8<sup>+</sup> 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. <span><span>ClinicalTrials.gov</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> identifier: <span><span>NCT03618641</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>.","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

GDF15 research from bench to bedside 从工作台到床边的 GDF15 研究

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-24 DOI: 10.1016/j.ccell.2024.10.002

Samuel N. Breit, David A. Brown, Vicky W.W. Tsai

引用次数: 0

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma 蛋白质基因组表面组研究发现 DLK1 是神经母细胞瘤的免疫治疗靶点

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-24 DOI: 10.1016/j.ccell.2024.10.003

Amber K. Hamilton, Alexander B. Radaoui, Matthew Tsang, Daniel Martinez, Karina L. Conkrite, Khushbu Patel, Simone Sidoli, Alberto Delaidelli, Apexa Modi, Jo Lynne Rokita, Maria V. Lane, Nicholas Hartnett, Raphael D. Lopez, Bo Zhang, Chuwei Zhong, Brian Ennis, Daniel P. Miller, Miguel A. Brown, Komal S. Rathi, Pichai Raman, Sharon J. Diskin

{"title":"A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma","authors":"Amber K. Hamilton, Alexander B. Radaoui, Matthew Tsang, Daniel Martinez, Karina L. Conkrite, Khushbu Patel, Simone Sidoli, Alberto Delaidelli, Apexa Modi, Jo Lynne Rokita, Maria V. Lane, Nicholas Hartnett, Raphael D. Lopez, Bo Zhang, Chuwei Zhong, Brian Ennis, Daniel P. Miller, Miguel A. Brown, Komal S. Rathi, Pichai Raman, Sharon J. Diskin","doi":"10.1016/j.ccell.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.10.003","url":null,"abstract":"Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlates with a super-enhancer. Immunofluorescence, flow cytometry, and immunohistochemistry show robust cell surface expression of DLK1. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells results in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"12 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488632","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 tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade 利用 CTLA4 阻断剂克服肺癌脑转移中的酪氨酸激酶抑制剂耐药性

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-17 DOI: 10.1016/j.ccell.2024.09.012

Minjie Fu, Jiaxu Zhao, Licheng Zhang, Zhewei Sheng, Xiaohui Li, Fufang Qiu, Yuan Feng, Muyuan You, Hao Xu, Jinsen Zhang, Rui Zeng, Yang Huang, Cheng Li, Wenhan Chen, Zheng Chen, Haibao Peng, Longzhi Li, Yonghe Wu, Dan Ye, Yudan Chi, Ying Mao

引用次数: 0

IL-1 signaling in aging and cancer: An inflammaging feedback loop unveiled IL-1 信号在衰老和癌症中的作用：揭示炎症反馈回路

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-10-17 DOI: 10.1016/j.ccell.2024.09.015

Mingyong Liu, Bo Zhu, Qi-Jing Li

引用次数: 0