In vitro 3D model of the immune-oncology stromal barrier for evaluating T-cell accumulation and cytotoxicity

However, few available in vitro experimental systems can assess T-cell infiltration into tumor tissues in a manner that structurally mimics the tumor tissue due to difficulties in controlling cell position. Here, we developed a stacked three-dimensional (3D) stromal tissue using a cell-assembled viscous tissues method.

Stromal tissues, including cancer-associated fibroblasts (CAFs), created a stromal barrier that prevented cytotoxic T cells from attacking cancer cells. Drug screening using the CAF model demonstrated that HDAC inhibitors promote T-cell infiltration and its combined effects and suppress extracellular matrix formation and CAF expression by acting on fibroblasts. Thus, the stromal barrier–inclusive co-culture model that partially reproduces CAF-induced cold tumors could facilitate the development of drugs that promote immune cell infiltration and cell-cell interaction studies.