Label-Free Deep Profiling of the Tumor Microenvironment

被引:20
|
作者
You, Sixian [1 ,2 ,7 ]
Chaney, Eric J. [1 ]
Tu, Haohua [1 ]
Sun, Yi [1 ,3 ]
Sinha, Saurabh [4 ,5 ,6 ]
Boppart, Stephen A. [1 ,2 ,3 ,5 ,6 ]
机构
[1] Univ Illinois, Beckman Inst Adv Sci & Technol, 405 North Mathews Ave, Urbana, IL 61801 USA
[2] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA
[3] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA
[4] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA
[5] Univ Illinois, Canc Ctr Illinois, Urbana, IL 61801 USA
[6] Univ Illinois, Carle Illinois Coll Med, Urbana, IL 61801 USA
[7] MIT, Elect Engn & Comp Sci, Cambridge, MA 02139 USA
关键词
IN-VIVO; EXTRACELLULAR VESICLES; SPATIAL HETEROGENEITY; GENERATION; CELLS; FLUORESCENCE; SENSITIVITY; MICROSCOPY;
D O I
10.1158/0008-5472.CAN-20-3124
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Label-free nonlinear microscopy enables nonperturbative visualization of structural and metabolic contrast within living cells in their native tissue microenvironment. Here a computational pipeline was developed to provide a quantitative view of the microenvironmental architecture within cancerous tissue from label-free nonlinear microscopy images. To enable single-cell and singleextracellular vesicle (EV) analysis, individual cells, including tumor cells and various types of stromal cells, and EVs were segmented by a multiclass pixelwise segmentation neural network and subsequently analyzed for their metabolic status and molecular structure in the context of the local cellular neighborhood. By comparing cancer tissue with normal tissue, extensive tissue reorganization and formation of a patterned cell-EV neighborhood was observed in the tumor microenvironment. The proposed analytic pipeline is expected to be useful in a wide range of biomedical tasks that benefit from single-cell, single-EV, and cell-to-EV analysis. Significance: The proposed computational framework allows label-free microscopic analysis that quantifies the complexity and heterogeneity of the tumor microenvironment and opens possibilities for better characterization and utilization of the evolving cancer landscape.
引用
收藏
页码:2534 / 2544
页数:11
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