hmLIGHT Enhances Vaccine Antitumor Effects by Facilitating T-cell Infiltration and Activation in the 4T1 Breast Cancer Model.

Abstract

Mounting evidence suggests that immunotherapies are promising strategies for fighting against cancers. However, the immunosuppressive tumor microenvironment (TME), insufficient lymphocytic infiltration, and poor immunogenicity hamper the broader implementation of immunotherapies. LIGHT, a member of the TNF superfamily, has been shown to recruit T cells into the TME, turning "cold" tumors into "hot" ones. Here, a human mutant LIGHT (hmLIGHT) protein has been obtained which successfully promoted the activation and proliferation of mouse CD8+ T cells via CD28-independent co-stimulatory activity. Moreover, direct intratumoral injection of VR-hmLIGHT remodeled the TME, enhanced CD8+ T-cell infiltration into tumors, and showed antitumor efficacy in 4T1 and CT26 tumor models. In addition, our previous studies of a DNA vaccine (OsFS) have shown promising antitumor activity. In this study, we evaluated a new combination of VR-hmLIGHT and OsFS to enhance efficacy in the 4T1 tumor model. The combined treatment has a remarkable antitumor effect, with a tumor inhibition rate of 70%, whereas OsFS and VR-hmLIGHT groups displayed 32% and 42% inhibition, respectively. These findings indicate the clinical potential of LIGHT as monotherapy or combination therapy.