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STING signaling can exert both tumor-suppressive and tumor-promoting effects. A distinction must, therefore, be made between IFN signaling (stimulation of interferon genes) and the promotion of autophagy. The IFN-independent functions of STING explain its tumor-promoting and prometastatic effects.
Intratumoral injection of the STING agonist cyclic di-GMP (CDG) in mice (TRAMPC2 model of prostate cancer) together with antibodies against CTLA-4, PD-1, and 4-1BB, also administered intratumorally, led to an enhanced therapeutic effect. Only CDG led to abscopal immunity.
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