FIGURE 1: STING agonist-induced effects on innate immune cells in the TME. Intratumoral injection of STING agonists induces repolarization of type-2 macrophages into type-1 macrophages, resulting in enhanced co-stimulation and differentiation of CD4⁺ and CD8⁺ T cells [39]. STING ligand-induced tumor cell death leads to the release of tumor-derived antigens and DNA, which are taken up by DCs, resulting in the release of type I IFNs and enhanced T cell activation [23][24][27]. Intratumoral injection of STING agonists results in the secretion of the chemokines CXCL9, CXCL10, and CXCL10, CXCL11, which are secreted by DCs and macrophages, respectively [37][41]. As a result, cytotoxic CD8⁺ T cells are recruited to the TME. STING agonists induces the secretion of type I IFN, leading to terminal differentiation of immature DCs and enhanced activation of DCs. Overall, intratumoral STING agonists injection leads to macrophage repolarization, DC cross-presentation, T cell trafficking, and DC maturation and activation, resulting in enhanced recruitment and activation of anti-tumor CD8⁺ T cells and improved tumor control.

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