Fig. 7: Comparison between LiSmore and STING agonist treatment.

STING agonists, such as cGAMP, have demonstrated promising antitumor efficacy; however, their use carries the risk of systemic inflammation due to excessive cytokine production and lacks specificity in tumor targeting. Furthermore, excessive cGAMP can induce T- and B-cell death and upregulate the expression of immunosuppressive genes, such as programmed death-ligand 1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1), counteracting its tumor-suppressive effects. These concerns can be addressed by developing a switchable STING activator, such as LiSmore, which utilizes light to reversibly trigger STING pathway activation, providing precise control over antitumor immunity. Local or systemic infusion of LiSmore-DCs allows for targeted STING activation through simple blue light stimulation. This precise control over STING activation leads to enhanced DC maturation and improved cross-presentation of tumor antigens, thereby priming effector T cells in tumor-draining lymph nodes to boost tumor cell killing. Additionally, LiSmore induces a systemic antitumor response through an abscopal effect, likely due to its ability to sustain STING pathway activation and elicit a more durable immune response. This unconventional strategy holds promise for improving cancer immunotherapies by harnessing the power of the STING pathway in a controlled and selective manner. Created by biorender.com.