Characterization of the tumor microenvironment by highly multiplexed microscopy

Malignant neoplasms are highly complex ecosystems consisting of tumor cells and the tumor microenvironment (TME), which is composed of structural elements (vessels, fibroblasts, extracellular matrix) and a wide variety of infiltrating immune cell types of the innate and adaptive immune systems. The TME is the main site of tumor cell-immune cell interactions and plays a critical role in antitumoral immunity. Immunotherapies can affect the interactions between immune cell types and tumor cells in the TME, boost immune responses, and lead to tumor elimination. Novel highly multiplexed microscopy techniques, which enable the detection of more than 50 simultaneous markers in tissues, facilitate the in-depth characterization of the TME at single-cell resolution in clinically relevant samples. Detailed knowledge about the cellular and spatial composition of the TME, the specific cell types and their functional properties, and cell-cell interactions-as revealed by highly multiplexed microscopy-will improve our understanding of immunotherapies' mechanisms of action and reveal new potential therapeutic targets and predictive biomarkers.