CAR-T therapy treatments have proven effective in patients with blood tumors, however, their efficacy in solid tumors has been limited due to a variety of factors, including the tumor microenvironment. For this reason, researchers used a 3D microfluidic model made from patient-derived organotypic tumor spheroids (PDOTS) to study the mechanisms of treatment resistance of CAR-T cells designed in particular to target B7-H3, a common antigen in solid tumor cancers. By inhibiting the function of TBK1, a gene previously associated with immune evasion, they were able to restore CAR-T cell activity, prevent dysfunction and increase T cell proliferation. The researchers also found that inhibiting or suppressing TBK1 made cancer cells more sensitive to immune cell targeting and killing. The results therefore suggest that targeting TBK1 could reduce treatment resistance and improve CAR T efficacy in solid tumor cells expressing B7-H3, and also demonstrate the feasibility and utility of using PDOTS to study tumor-immune cell interactions.
