Cancer progression is significantly influenced by the complex interactions within the tumor microenvironment (TME). Immune cells, in particular, play a critical role by infiltrating tumors from the circulation and surrounding lymphoid tissues in an attempt to control their spread. However, they often fail in this task. Current in vivo and in vitro preclinical models struggle to fully capture these intricate interactions affecting our ability to understand immune evasion and predict drugs behaviour in the clinic. To address this challenge, biofabrication and particularly 3D bioprinting has emerged as a promising tool for modeling both tumors and the immune system. Its ability to incorporate multiple cell types into 3D matrices, enable tissue compartmentalization with high spatial accuracy, and integrate vasculature makes it a valuable approach. Nevertheless, limited research has focused on capturing the complex tumor-immune interplay in vitro. This review highlights the composition and significance of the TME, the architecture and function of lymphoid tissues, and innovative approaches to modeling their interactions in vitro, while proposing the concept of an extended TME.
