Targeting Tumor‐Immune Microenvironment with Organoid and Organ‐on‐a‐Chip: An Updated Review

Abstract A better understanding of the tumor‐immune microenvironment (TIME) is essential for identifying the initial triggers of cancer progression and developing effective cancer treatment strategies. Organoid, organ‐on‐a‐chip (OoC), and integrated organoid‐on‐a‐chip platforms have emerged as powerful tools for recapitulating the tumor microenvironment (TME) by incorporating its critical components, including cancer cells, stromal cells, extracellular matrix, and signaling molecules. These systems have significantly advanced research on the TIME, facilitating the study of cancer from initiation to progression and the evaluation of therapeutic regimens, particularly in cancer immunotherapy. Therefore, this review focuses on the up‐to‐date advancements in modeling the TIME based on organoid, OoC and organoid‐on‐a‐chip technologies. The review starts with an overview of the constituents and function of the TIME. It then examines the strategies to replicate the TIME using these models. Finally, it highlights the future prospects and challenges that need to be addressed to develop more functional in vitro models of the TIME.