TY - JOUR
T1 - Unraveling the Complexity of the Cancer Microenvironment With Multidimensional Genomic and Cytometric Technologies
AU - de Vries, Natasja L.
AU - Mahfouz, Ahmed
AU - Koning, Frits
AU - de Miranda, Noel F.C.C.
PY - 2020
Y1 - 2020
N2 - Cancers are characterized by extensive heterogeneity that occurs intratumorally, between lesions, and across patients. To study cancer as a complex biological system, multidimensional analyses of the tumor microenvironment are paramount. Single-cell technologies such as flow cytometry, mass cytometry, or single-cell RNA-sequencing have revolutionized our ability to characterize individual cells in great detail and, with that, shed light on the complexity of cancer microenvironments. However, a key limitation of these single-cell technologies is the lack of information on spatial context and multicellular interactions. Investigating spatial contexts of cells requires the incorporation of tissue-based techniques such as multiparameter immunofluorescence, imaging mass cytometry, or in situ detection of transcripts. In this Review, we describe the rise of multidimensional single-cell technologies and provide an overview of their strengths and weaknesses. In addition, we discuss the integration of transcriptomic, genomic, epigenomic, proteomic, and spatially-resolved data in the context of human cancers. Lastly, we will deliberate on how the integration of multi-omics data will help to shed light on the complex role of cell types present within the human tumor microenvironment, and how such system-wide approaches may pave the way toward more effective therapies for the treatment of cancer.
AB - Cancers are characterized by extensive heterogeneity that occurs intratumorally, between lesions, and across patients. To study cancer as a complex biological system, multidimensional analyses of the tumor microenvironment are paramount. Single-cell technologies such as flow cytometry, mass cytometry, or single-cell RNA-sequencing have revolutionized our ability to characterize individual cells in great detail and, with that, shed light on the complexity of cancer microenvironments. However, a key limitation of these single-cell technologies is the lack of information on spatial context and multicellular interactions. Investigating spatial contexts of cells requires the incorporation of tissue-based techniques such as multiparameter immunofluorescence, imaging mass cytometry, or in situ detection of transcripts. In this Review, we describe the rise of multidimensional single-cell technologies and provide an overview of their strengths and weaknesses. In addition, we discuss the integration of transcriptomic, genomic, epigenomic, proteomic, and spatially-resolved data in the context of human cancers. Lastly, we will deliberate on how the integration of multi-omics data will help to shed light on the complex role of cell types present within the human tumor microenvironment, and how such system-wide approaches may pave the way toward more effective therapies for the treatment of cancer.
KW - cancer microenvironment
KW - data integration
KW - immunophenotyping
KW - mass cytometry
KW - multi-omics
KW - single-cell
KW - spatial analysis
UR - http://www.scopus.com/inward/record.url?scp=85089086645&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.01254
DO - 10.3389/fonc.2020.01254
M3 - Review article
AN - SCOPUS:85089086645
SN - 2234-943X
VL - 10
SP - 1
EP - 15
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1254
ER -