Tumor Immune Engineering: Developing In Vitro Assays to Understand the Tumor-Immune Crosstalk

Interaction between a growing tumor and the host immune system has various facets, which eventually influence the fate of both the tumor and the host. In the last decade, multiple efforts have been undertaken to mimic the heterogeneous consortium of tumors to comprehend tumor biology. Understanding the tumor-stromal or tumor-immune crosstalk is also crucial for screening and pre-clinical evaluation of therapeutic candidates. The development of human-relevant and physiologically similar models is the need of the hour to bridge the gap. Existing models relevant to tissue engineering, including porous scaffolds, hydrogel, and fibrous mats, are widely utilized to recapitulate the tumor microenvironment. In spite of their inherent limitations, they are employed to study tumor-immune interactions in the past. In the recent decade, emerging techniques such as Microfluidics, organ on a chip, and 3D Bioprinting have been used prevalently to mimic the heterogeneous landscape of tumors. This review is intended to discuss the current developments in the field of in vitro 3D tumor models while focusing on the tumor-immune crosstalk. Furthermore, the theoretical and practical limitations of the conventional model mimicking the tumorimmune crosstalk and the need for 'out of the box' ideas by converging the existing models are highlighted.