earticle

영어

Several advances in anticancer therapy have demonstrated significant improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, it remains a challenge because only a small percentage of respondents have responded. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. Here, we propose an in vitro 3D tumor model with clusters of colorectal cancer (CRC) cells around perfusable vascular networks to evaluate immune cell-mediated cytotoxicity against cancer cells. A 3D injection-molded co-culture model consists of 28 microwells where identical vascularized cancer models can be formed in separate wells. It allows robust hydrogel patterning, resulting in high-throughput experiments. Compared to the polydimethylsiloxane (PDMS)-based microfluidic devices, our devices allowed a greater number of experiments to be conducted. A permeability test was also conducted to confirm the characteristics of the tumor vasculature. Primary natural killer (NK) cells were introduced into a tumor vascularized network and monitored using live-cell imaging. The extravasation, migration, and cytotoxic activity of six types of CRC cell lines were examined. Based on the consensus molecular subtypes (CMS) of CRC with distinct immune responses, CMS1 cancer cells were most susceptible to NK cell cytotoxicity. This study indicates the potential of our vascularized tumor model in assessing the responses to adoptive cell therapy by understanding the various steps involved in the immune response.