GSTDTAP  > 资源环境科学
DOI10.1038/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
ISSN2041-1723
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
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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
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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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