The cGAS-STING pathway plays a critical role in activating dendritic cells (DCs) to sense immunogenic tumors. Type I interferons (IFN-I) are essential for antiviral and anticancer immunity, and their signaling is crucial in various cancer therapies. The cGAS-STING pathway activates IFN-I production by detecting cytoplasmic DNA, which is essential for immune responses. STING can also enhance anticancer immunity through autophagy, inflammation, and glycolysis, independent of IFN-I. These findings highlight the importance of understanding the cGAS-STING-IFN-I signaling axis in cancer therapy and the challenges in developing STING agonist drugs. DCs are vital in antigen presentation and the tumor immune cycle, which involves T-cell infiltration and tumor cell elimination. Different DC subtypes, such as conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have distinct roles in immune responses. cDCs are crucial for antigen cross-presentation and activating CD8+ T cells, while pDCs are important for IFN-I production and antiviral immunity. Tumor-infiltrating DCs (TIDCs) can influence antitumor immune responses, but their functionality is often impaired in the tumor microenvironment (TME). The innate activation of DCs is mediated by pattern recognition receptors (PRRs) such as TLRs, RIG-I/MDA5, and cGAS-STING. These pathways lead to the production of IFN-I and other cytokines, which enhance T-cell activation and antitumor immunity. The cGAS-STING pathway is involved in autophagy, endoplasmic reticulum stress, and metabolic regulation, contributing to immune responses. STING can also activate non-canonical autophagy and promote immune cell infiltration in the TME. The cGAS-STING-IFN-I axis is a key regulator in the cancer immune cycle, influencing tumor cell death, immune cell activation, and antitumor immunity. IFN-I promotes DC maturation and antigen presentation, enhancing T-cell responses. STING agonists can activate IFN-I-independent pathways, such as autophagy and inflammation, to improve antitumor immunity. However, the activation of STING can also lead to T-cell apoptosis, highlighting the need for careful dosing in cancer immunotherapy. Recent advances in clinical drug development targeting the cGAS-STING-IFN-I axis include the use of STING agonists, which have shown promise in cancer treatment. These drugs can enhance immune responses through various mechanisms, including IFN-I production and autophagy. The development of IFN-I drugs, such as PEG-IFN and antibody-conjugated IFN-I, has also shown potential in improving treatment outcomes. Overall, the cGAS-STING-IFN-I axis is a criticalThe cGAS-STING pathway plays a critical role in activating dendritic cells (DCs) to sense immunogenic tumors. Type I interferons (IFN-I) are essential for antiviral and anticancer immunity, and their signaling is crucial in various cancer therapies. The cGAS-STING pathway activates IFN-I production by detecting cytoplasmic DNA, which is essential for immune responses. STING can also enhance anticancer immunity through autophagy, inflammation, and glycolysis, independent of IFN-I. These findings highlight the importance of understanding the cGAS-STING-IFN-I signaling axis in cancer therapy and the challenges in developing STING agonist drugs. DCs are vital in antigen presentation and the tumor immune cycle, which involves T-cell infiltration and tumor cell elimination. Different DC subtypes, such as conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have distinct roles in immune responses. cDCs are crucial for antigen cross-presentation and activating CD8+ T cells, while pDCs are important for IFN-I production and antiviral immunity. Tumor-infiltrating DCs (TIDCs) can influence antitumor immune responses, but their functionality is often impaired in the tumor microenvironment (TME). The innate activation of DCs is mediated by pattern recognition receptors (PRRs) such as TLRs, RIG-I/MDA5, and cGAS-STING. These pathways lead to the production of IFN-I and other cytokines, which enhance T-cell activation and antitumor immunity. The cGAS-STING pathway is involved in autophagy, endoplasmic reticulum stress, and metabolic regulation, contributing to immune responses. STING can also activate non-canonical autophagy and promote immune cell infiltration in the TME. The cGAS-STING-IFN-I axis is a key regulator in the cancer immune cycle, influencing tumor cell death, immune cell activation, and antitumor immunity. IFN-I promotes DC maturation and antigen presentation, enhancing T-cell responses. STING agonists can activate IFN-I-independent pathways, such as autophagy and inflammation, to improve antitumor immunity. However, the activation of STING can also lead to T-cell apoptosis, highlighting the need for careful dosing in cancer immunotherapy. Recent advances in clinical drug development targeting the cGAS-STING-IFN-I axis include the use of STING agonists, which have shown promise in cancer treatment. These drugs can enhance immune responses through various mechanisms, including IFN-I production and autophagy. The development of IFN-I drugs, such as PEG-IFN and antibody-conjugated IFN-I, has also shown potential in improving treatment outcomes. Overall, the cGAS-STING-IFN-I axis is a critical