Table 2.

Description and characterization of the spatial architecture of the tumor immune microenvironment (TIME)

Components	Definition	Detection methods	Detecting characteristics
Location of immune cells	Identification and quantification of immune cells in different compartments of tumor	H&E staining, digital pathology	Morphological differences; visual distinction of tumor compartments (i.e., sTILs, iTILs)
		Probe-based in situ imaging	Cellular markers
		Spatial omics	Expression signature
Distance between immune cells	The shortest distance between cells	Cellular-resolution imaging and analysis algorithms	The recognition and identification of cells and their surrounding cells; determination of distance between cells
	Density of immune cells in a certain area around the tumor cell
Distribution of immune regulators	Compartment-based distribution	Probe-based in situ imaging and/or spatial omics	Spatial protein or mRNA expression at cellular or subcellular resolution
	Cell-specific spatial expression and co-location
	Spatial proximity of paired receptor and ligand
Identification of specific spatial patterns	Robust spatial architecture of immune cells with specific aggregation and distribution patterns (i.e., TLSs, peri-vascular niches)	Digital pathology	Visual spatial arrangement features of cells
		Immunohistochemistry	Pattern-specific marker
		Probe-based in situ imaging and/or spatial omics	Pattern-specific marker at cellular or subcellular resolution

TILs, tumor infiltrated lymphocytes; TLSs, tertiary lymphoid structures