Table 1 Strategies used to target MIC-specific cGAS/STING signaling pathway in TIME
From: Targeting cGAS/STING signaling-mediated myeloid immune cell dysfunction in TIME
Therapeutic approaches in tumor type | Status (clinical or preclinical) | Specific MIC | Mechanism |
|---|---|---|---|
Chemotherapy + PCIs in osteosarcoma [160] | Preclinical (Mouse model) | Macrophages, DCs | Increase type 1 IFN and IL-18 release and decrease LAT2 expression on tumor cells |
Peptide nanotube + STING agonist (c-di-GMP-PNT) in melanoma [162] | Preclinical (Mouse model) | Macrophages | Induce STING-dependent type 1 IFN, IL-6, IL-1β and TNF-α release as well as am antitumor CD4+ and CD8+ T-cell based immune response |
S100 (a STING agonist) + ICIs melanoma and colon cancer [164] | Preclinical (Mouse model) | TAMs and DCs | Type 1 IFN generation |
cGAMP-VLPs in mouse melanoma and bladder cancer [165] | Preclinical (Mouse model) | cDC1s | Increases antitumor cytotoxic T cells, decreases Tregs and works synergistically with ICIs better than S100 |
Radiation + cGAMP treatment in mouse model of colorectal cancer [90] | Preclinical (Mouse model) | DCs | Type 1 IFN |
Cancer vaccine (STINGVAX, a combination of CDNs and GM-CSF) in mouse model of melanoma, colon cancer, upper aerodigestive squamous cell carcinoma, and pancreatic carcinoma [171] | Preclinical (Mouse model) | DCs | Upregulate PD-L1, increase DC activation via STING activation |
Radiotherapy + STING activating nano vaccine in melanoma, colon cancer and human papilloma virus-E6/E7 tumor (cervical cancer) models [143] | Preclinical (Mouse model) | Non-specific | Increase CD8+ T-cells in primary tumors |
Cell free anticancer vaccine in mouse models of melanoma and colon cancer [179] | Preclinical (Mouse model) | DCs | Uses tumor derived MPs to transfer DNA fragments to DCs, thus activating cGAS/STING dependent acute type 1 IFN release |
TTfields in GBMs [192] | Clinically approved for GBMs | DCs | cGAS/STING-dependent DCs activation induces cytotoxic T cell activation and clonal expansion |
Tumor-derived exosomes as cancer vaccines, including ExoSTING, an engineered EV with CDN in mouse models of melanoma, colon cancer, and lymphoma [200] | Preclinical (Mouse model) | DCs and macrophages | Transfer dsDNA to DCs to activate type 1 IFN production and increase antitumor CD8+ T-cell response |
STING agonist (di-ABZI) + IDO inhibitor in mouse models of colorectal cancer [201] | Preclinical (Mouse model) | DCs, MDSCs | Recruit DCs and CD8 + T-cells, inhibits MDSCs |
STING agonist SHR1032 in murine colorectal cancer and acute myeloid leukemia [202] | Preclinical (Mouse model) | Macrophages, DCs | Reprogram M2 macrophages to M1, enhance antitumor function of DCs via cGAS/STING dependent signaling pathway, coordinate anticancer PARP-1 function |
Mn2+  + ICIs mouse models of melanoma and colorectal cancer [208] | Preclinical (Mouse model) | Macrophages, DCs | Mn [2]+ activates cGAS/STING signaling, Promotes CD8+ T-cell differentiation & activation, NK cell activation, and memory CD8+ T-cell differentiation |
Metalloimmunotherapy (ONc-Mn-A-malF127) in mouse model of colorectal cancer [210] | Preclinical (Mouse model) | DCs in TIME | Activates STING signaling in DCs, which migrate to tumor-derived lymph nodes and activate antitumor T cells to kill tumor cells |
Microfabricated PLGA encapsulating cGAMP or other STING agonists in mouse model of melanoma and late-stage breast cancer [180] | Preclinical (Mouse model) | MICs in TIME along with lymphocytes | Activates STING, repolarizes M2 macrophages to M1s, induces maturation of DCs to increase their antigen presentation capacity |
Zym:Ad conjugate encoding IRF3 in mouse model of melanoma [181] | Preclinical (Mouse model) | MICs in TIME | Repolarizes M2 macrophages to M1s |
ProIFN or masked type 1 IFN-Fc in mouse models of melanoma, colon, and lung cancer [182, 183] | Preclinical (Mouse model) | MICs in TIME | Increases DC cross-priming, CD8+T cell antitumor activity |