학술논문
Molecular, Metabolic, and Subcellular Mapping of the Tumor Immune Microenvironment via 3D Targeted and Non-Targeted Multiplex Multi-Omics Analyses.
Document Type
Academic Journal
Author
Ferri-Borgogno S; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Burks JK; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Seeley EH; Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA.; McKee TD; Pathomics, Inc., Toronto, ON M4C 3K2, Canada.; Stolley DL; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Basi AV; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Gomez JA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Gamal BT; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Ayyadhury S; Pathomics, Inc., Toronto, ON M4C 3K2, Canada.; Lawson BC; Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Yates MS; Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA.; Birrer MJ; Winthrop P. Rockefelle Cancer Institute, The University of Arkanasas for Medical Sciences, Little Rock, AR 72205, USA.; Lu KH; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Mok SC; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2072-6694
Abstract
Most platforms used for the molecular reconstruction of the tumor-immune microenvironment (TIME) of a solid tumor fail to explore the spatial context of the three-dimensional (3D) space of the tumor at a single-cell resolution, and thus lack information about cell-cell or cell-extracellular matrix (ECM) interactions. To address this issue, a pipeline which integrated multiplex spatially resolved multi-omics platforms was developed to identify crosstalk signaling networks among various cell types and the ECM in the 3D TIME of two FFPE (formalin-fixed paraffin embedded) gynecologic tumor samples. These platforms include non-targeted mass spectrometry imaging (glycans, metabolites, and peptides) and Stereo-seq (spatial transcriptomics) and targeted seqIF (IHC proteomics). The spatially resolved imaging data in a two- and three-dimensional space demonstrated various cellular neighborhoods in both samples. The collection of spatially resolved analytes in a voxel (3D pixel) across serial sections of the tissue was also demonstrated. Data collected from this analytical pipeline were used to construct spatial 3D maps with single-cell resolution, which revealed cell identity, activation, and energized status. These maps will provide not only insights into the molecular basis of spatial cell heterogeneity in the TIME, but also novel predictive biomarkers and therapeutic targets, which can improve patient survival rates.