Table 1.

Summary of approaches for classification of the tumor immune microenvironment (TIME).

Study	Algorithm	Data type used	Brief description	Advantages	Drawbacks
33	ABSOLUTE	DNA copy number array	Estimates percent of tumor cells within the TIME.	Predicts tumor purity.	Only provides information on tumoral components. No information on non-tumoral regions.
34	ESTIMATE	Gene expression data	Estimates tumor cellularity and proportion of stromal and immune cells present in TIME.	Provides Immune, Stromal, ESTIMATE, and tumor purity scores. Optimized for solid tumors including brain tumors.	Limited application in hematopoietic and stromal tumors. No quantification of individual immune cell-types.
28	Immunoscore	Gene expression data	Quantifies CD3 and CD8 T-cell infiltration at the tumor core and invasive margin.	Used extensively to classify solid tumors as “immune hot, cold, or altered” Validated to have additive value to TNM staging in colorectal cancer. Found to have value in predicting response to immunotherapy.	Limited by cell types assessed. More holistic markers are favored.
38	CIBERSORT	Gene expression data	Detects 22 different human immune cell types and provides quantification with high sensitivity and specificity.	Provides a more comprehensive analysis of the TIME. Allow for clustering of immune cell types and correlations of cell types with other biomarkers and signatures.	Not a summary metric.
96	xCell	Gene expression data	Identifies 64 different cell types, both immune and stromal using a combination of gene set enrichment and deconvolution approaches.	Provides a large feature set for clustering and correlation. Comprehensive profiling of cell types in the TIME.	Not a summary metric.
39	Tumor Inflammation Signature	Gene expression data	Measures level of tumor microenvironment inflammation through the analysis of 18 genes. Originally introduced in the context of clinical trials as a biomarker for immune-checkpoint blockade response.	Provides a metric for inflammatory state. Clinically relevant for novel therapeutics.	Does not provide information on specific immune composition of TIME.