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DOI | 10.1038/s41467-018-06765-2 |
EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer | |
Wang, Li1,2,3; Saci, Abdel4; Szabo, Peter M.4; Chasalow, Scott D.4; Castillo-Martin, Mireia5; Domingo-Domenech, Josep6,7; Siefker-Radtke, Arlene8; Sharma, Padmanee8; Sfakianos, John P.9; Gong, Yixuan10; Dominguez-Andres, Ana6,7; Oh, William K.10; Mulholland, David10; Azrilevich, Alex4; Hu, Liangyuan11; Cordon-Cardo, Carlos5; Salmon, Helene12; Bhardwaj, Nina10; Zhu, Jun1,2,3,10; Galsky, Matthew D.10 | |
2018-08-29 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information. We further demonstrate that non-hematopoietic stromal cells are a major source of EMT-related gene expression in bulk urothelial cancer transcriptomes. Finally, using a cohort of patients with metastatic urothelial cancer treated with a PD-1 inhibitor, nivolumab, we demonstrate that in patients with T-cell infiltrated tumors, higher EMT/stroma-related gene expression is associated with lower response rates and shorter progression-free and overall survival. Together, our findings suggest a stroma-mediated source of immune resistance in urothelial cancer and provide rationale for co-targeting PD-1 and stromal elements. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000442998800008 |
WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; COMPREHENSIVE MOLECULAR CHARACTERIZATION ; TUMOR MICROENVIRONMENT ; BLADDER-CANCER ; SINGLE-ARM ; FIBROBLASTS ; MULTICENTER ; CARCINOMA ; SUBTYPES ; THERAPY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
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/204044 |
专题 | 资源环境科学 |
作者单位 | 1.Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA; 2.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA; 3.Sema4, Stamford, CT 06902 USA; 4.Bristol Myers Squibb, Princeton, NJ 08543 USA; 5.Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA; 6.Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Oncol, Philadelphia, PA 19107 USA; 7.Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA; 8.Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA; 9.Icahn Sch Med Mt Sinai, Dept Urol, New York, NY 10029 USA; 10.Icahn Sch Med Mt Sinai, Dept Med, Div Hematol Oncol, Tisch Canc Inst, New York, NY 10029 USA; 11.Icahn Sch Med Mt Sinai, Tisch Canc Inst, Ctr Biostat, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA; 12.Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA |
推荐引用方式 GB/T 7714 | Wang, Li,Saci, Abdel,Szabo, Peter M.,et al. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Wang, Li.,Saci, Abdel.,Szabo, Peter M..,Chasalow, Scott D..,Castillo-Martin, Mireia.,...&Galsky, Matthew D..(2018).EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer.NATURE COMMUNICATIONS,9. |
MLA | Wang, Li,et al."EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer".NATURE COMMUNICATIONS 9(2018). |
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