Synergy of a STING agonist and an IL-2 superkine in cancer immunotherapy against MHC I–deficient and MHC I ⁺ tumors

Significance Immunotherapy provides long-term remissions in numerous types of cancer but is ineffective in most tumors with poor immune cell infiltrates or lacking T cell epitopes or MHC I molecules. Agents that activate the STING protein showed promise in several MHC I + and MHC-deficient tumor models in mice, where they induced powerful antitumor CD8 + T cell and natural killer (NK) cell responses, respectively. They were less effective in numerous other tumor models and yielded mixed results in the clinic in human patients. This report demonstrates strong synergy between a STING agonist and an IL-2 superkine in effectively curing difficult-to-treat MHC-deficient and MHC-positive tumor models in mice by mobilizing T cells and NK cells. This combination therapy shows considerable promise for clinical application.