STING Protein-Based In Situ Vaccine Synergizes CD4⁺ T, CD8⁺ T, and NK Cells for Tumor Eradication.

ABSTRACT: Stimulator of interferon genes (STING) signaling is a promising target in cancer immunotherapy, with many ongoing clinical studies in combination with immune checkpoint blockade (ICB). Existing STING-based therapies largely focus on activating CD8⁺ T cell or NK cell-mediated cytotoxicity, while the role of CD4⁺ T cells in STING signaling has yet to be extensively studied in vivo. Here, a distinct CD4-mediated, protein-based combination therapy of STING and ICB as an in situ vaccine, is reported. The treatment eliminates subcutaneous MC38 and YUMM1.7 tumors in 70-100% of mice and protected all cured mice against rechallenge. Mechanistic studies reveal a robust T_H 1 polarization and suppression of T_reg of CD4⁺ T cells, followed by an eff

SUBMITTER: He Y 

PROVIDER: S-EPMC10964211 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature