Table 2 Description and characterization of the spatial architecture of the tumor immune microenvironment (TIME)

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