Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aau0135 |
T cell stemness and dysfunction in tumors are triggered by a common mechanism | |
Vodnala, Suman Kumar1,2; Eil, Robert1,2,3; Kishton, Rigel J.1,2; Sukumar, Madhusudhanan1,2; Yamamoto, Tori N.1,2,4; Ngoc-Han Ha5; Lee, Ping-Hsien1,2; Shin, MinHwa5,14; Patel, Shashank J.1,2,15; Yu, Zhiya1,2; Palmer, Douglas C.1,2; Kruhlak, Michael J.6; Liu, Xiaojing7; Locasale, Jason W.7; Huang, Jing5; Roychoudhuri, Rahul8; Finkel, Toren9; Klebanoff, Christopher A.10,11,12,13; Restifo, Nicholas P.1,2 | |
2019-03-29 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 363期号:6434页码:1417-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; England; South Korea |
英文摘要 | A paradox of tumor immunology is that tumor-infiltrating lymphocytes are dysfunctional in situ, yet are capable of stem cell-like behavior including self-renewal, expansion, and multipotency, resulting in the eradication of large metastatic tumors. We find that the overabundance of potassium in the tumor microenvironment underlies this dichotomy, triggering suppression of T cell effector function while preserving stemness. High levels of extracellular potassium constrain T cell effector programs by limiting nutrient uptake, thereby inducing autophagy and reduction of histone acetylation at effector and exhaustion loci, which in turn produces CD8(+) T cells with improved in vivo persistence, multipotency, and tumor clearance. This mechanistic knowledge advances our understanding of T cell dysfunction and may lead to novel approaches that enable the development of enhanced T cell strategies for cancer immunotherapy. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000462738000028 |
WOS关键词 | LINEAGE RELATIONSHIP ; EXPRESSION ANALYSIS ; ACETYL-COENZYME ; EFFECTOR ; DIFFERENTIATION ; IMMUNOTHERAPY ; CANCER ; MODULATION ; SURVIVAL ; NECROSIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201088 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.NCI, Surg Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA; 2.NCI, Ctr Cell Based Therapy, Bethesda, MD 20892 USA; 3.Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA; 4.Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA; 5.NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA; 6.NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA; 7.Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA; 8.Babraham Inst, Babraham Res Campus, Cambridge, England; 9.Univ Pittsburgh, Dept Med, Sch Med, Aging Inst, 930 Scaife Hall, Pittsburgh, PA 15261 USA; 10.Parker Inst Canc Immunotherapy, New York, NY 10065 USA; 11.Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA; 12.Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA; 13.Cornell Univ, Weill Cornell Med Coll, New York, NY 10065 USA; 14.Korea Univ, Dept Biochem & Mol Biol, Coll Med, Seoul, South Korea; 15.Boehringer Ingelheim Pharmaceut Inc, Dept Canc Immunol & Immune Modulat, 90 E Ridge POB 368, Ridgefield, CT 06877 USA |
推荐引用方式 GB/T 7714 | Vodnala, Suman Kumar,Eil, Robert,Kishton, Rigel J.,et al. T cell stemness and dysfunction in tumors are triggered by a common mechanism[J]. SCIENCE,2019,363(6434):1417-+. |
APA | Vodnala, Suman Kumar.,Eil, Robert.,Kishton, Rigel J..,Sukumar, Madhusudhanan.,Yamamoto, Tori N..,...&Restifo, Nicholas P..(2019).T cell stemness and dysfunction in tumors are triggered by a common mechanism.SCIENCE,363(6434),1417-+. |
MLA | Vodnala, Suman Kumar,et al."T cell stemness and dysfunction in tumors are triggered by a common mechanism".SCIENCE 363.6434(2019):1417-+. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论