Targeted regulation of cytokines expression with a portable smart light-controllable device for tumor immunotherapy

As the first type of tumor immunotherapy drugs, cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, the application of cytokines for tumor immunotherapy was still limited to their short half-time, narrow therapeutic window, and undesired side effects. Here, we constructed a portable smart light-controllable (PSLC) device to address this issue. By combining the PSLC device and light-switchable gene modules, it is theoretically possible to regulate the cytokines expressed within target tumors by optical remote control. Then, cytokine interferon-γ (IFN-γ) and chemokine CXCL10, two essential immune regulatory molecules that play crucial roles in immunotherapy, are selected to test this system. To investigate whether light-induced cytokines may affect the tumor microenvironment, we established three animal tumor models, including single-tumor bearing DBA/2 mice with engineered P815-IFNγ cells or P815-M cells (control), and double-tumor bearing DBA/2 mice with engineered P815-IFNγ cells and P815-M cells (control). Each animal model is divided into two groups (3 mice/group), the dark group (as control ) and the light group. After illumination, all the tumor samples were resected from animals and quickly frozen with liquid nitrogen for RNA-seq, to compare the gene expression profile between the cytokines release group and the normal group.