Emerging approaches to study cell–cell interactions in tumor microenvironment

Cell–cell interactions are of crucial importance for tissue formation, homeostasis, regeneration processes, and immune response. Recent studies underlined contribution of cell–cell interaction in tumor microenvironment (TME) for tumor progression and metastasis. Cancer cells modify the host cells to tumor-supportive traits, and the modified host cells contribute to tumor progression by interacting with cancer cells and further modifying other normal cells. However, the complex interaction networks of cancer cells and host cells remained largely unknown. Recent advances in high throughput microscopy and single cells-based molecular analyses have unlocked a new era for studying cell–cell interactions in the complex tissue microenvironment at the resolution of a single cell. Here, we review various model systems and emerging experimental approaches that are used to study cell–cell interactions focusing on the studies of TME. We discuss strengths and weaknesses of each model system and each experimental approach, and how upcoming approaches can solve current fundamental questions of cell–cell interactions in TME.