A tumor on a chip for studying immune-cell infiltration into tumor under chemo/immunotherapy treatments

Abstract

The combo treatment of chemo/immunotherapy is a promising method in treating cancer patients. The results of Keynote-189 phase III clinical trial showed that chemotherapy drug plus immunotherapy drug reduced mortality compared with chemotherapy drug alone, in which the underlying mechanism has not been well demonstrated. The treatment combination also needs to be tuned for each patient, i.e., personalized medicine. Tumor-on-a-chip aims to mimic the tumor microenvironment (TME) with an in-vitro lung cancer-immune model to provide a potential solution for this application. Gelatin methacryloyl (GelMA)-cancer cells were driven on the ITO electrode track using liquid dielectrophoresis (LDEP) to form the tumor-like hydrogel. Jurkat T cells surrounded the solidified GelMA-A549 cells, resembling the cancer-immune microenvironment. The immune-cell infiltration phenomena of Jurkat T cells into the tumor were activated and enhanced via either IL-1β-treated A549 cells or atezolizumab (immune drugs) on the tumor lab chip. The death of cancer cells significantly increased ∼35% after chemo/immunotherapy combination treatment compared with the single treatment. The distribution of dead cancer cells treated with chemo/immunotherapy revealed their distinct theoretical mechanisms, indicating the promising application of this tumor lab chip for cancer patients in personalized medicine treatments.