Multi-Omics Profiling of the Tumor Microenvironment

All solid tumors and many hematological malignancies grow and proliferate in a tumor microenvironment (TME), a spectrum of continuous and highly dynamic interactions with different immune and stromal cells. This ecosystem contributes to the extensive heterogeneity that exists between and within cancer patients. Understanding the characteristics of this intricate network could significantly improve cancer prognosis, as was demonstrated already for a subset of patients by the advent of immunotherapies (including monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor (CAR) T cells. The development of multimodal omics technologies has allowed researchers to document and characterize the TME at single-cell resolution, which provides an unprecedent opportunity to understand the full complexity of the tumor microenvironment. In this chapter, we highlight the paradigm shift that has brought the TME to the forefront of cancer research and discuss its composition. In addition, we summarize the available multimodal single-cell omics methods that allow studying the TME from different angles, as well as their advantages and limitations. We discuss computational analysis tools, data integration, and methods to specifically study crosstalk between TME components. Finally, we touch upon the implications of studying the TME for ongoing or future clinical studies and how these can lead to more effective treatments for cancer patients.