RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access novel therapeutic biomarkers in the TME. Advanced computational methods are making it possible to resolve the composition of the tumor immune infiltrate, infer the immunological phenotypes of those cells, and assess the immune receptor repertoire in RNA-seq data. These immunological characterizations have increasingly important implications for guiding immunotherapy use. Here, we highlight recent studies that demonstrate the potential utility of RNA-seq in clinical settings, review key computational methods used for characterizing the TME for precision cancer immunotherapy, and discuss important considerations in data interpretation and current technological limitations.

Highlights:

-Cancer immunotherapy is a promising therapeutic area with the potential to impact a larger population of patients.

-Clinical adoption of RNA sequencing has potential to reveal novel prognostic or predictive biomarkers and expand the number of patients who can benefit from cancer immunotherapy.

-Algorithmic developments in RNA data allow for unprecedented profiling of the composition, specificity, and phenotype of the tumor immune response in a single assay.

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