Search

DNA sensor proteins play an important role in transducing DNA signals to induce immune responses that initiate inflammation or clear pathogens. It has been previously shown that several DNA sensors are involved in regulating tumor biology and/or cancer immunology. However, a systemic analysis of DNA sensor expression and its correlation with prognosis has not been conducted. Here, we analyzed messenger RNA expression and protein abundance in liver cancer databases and found that the genes of 5 DNA sensors (POLR3A, PRKDC, DHX9, cGAS, and MRE11) were consistently upregulated in tumor tissue. Moreover, the expression of these DNA sensor genes correlated with patient survival. Using a gene alterations analysis, we discovered that patients with genetically altered DNA sensors had significantly lower survival compared with an unaltered group. Furthermore, receiver-operating characteristic curves confirmed that the signatures of the 5 DNA sensors were independent prognostic factors in hepatocellular carcinoma. Tumor-infiltrating immune cell analysis revealed that expression of all 5 DNA sensors correlated with the amount of B cells, CD8 T cells, CD4 T cells, Tregs, DCs, Mϕs, and neutrophils. Surprisingly, 4 of the DNA sensors (POLR3A, PRKDC, DHX9, and MRE11) were inversely correlated with the amount of γδ T cells. Gene set enrichment analysis showed that all 5 DNA sensor genes were enriched for oxidative phosphorylation and xenobiotic metabolism. These results suggest that expression of these DNA sensors is associated with a unique immune profile and metabolic regulation in hepatocellular carcinoma.

New strategies targeting STING proteins appear promising for eliciting immunotherapeutic responses. Activation of the STING pathway under the right circumstances can drive dendritic cell maturation, antitumor macrophage differentiation, T-cell initiation and activation, natural killer cell activation, vascular reprogramming, and/or cancer cell death, leading to immune-mediated tumor elimination and generation of antitumor immune memory. However, activation of the STING signaling pathway is complicated in tumor immunity. On one hand, STING signaling was found to promote tumor growth. On the other hand, the cGAS-STING pathway has great potential for regulating antitumor immunity. The development of activators of the cGAS-STING pathway may profoundly change tumor immunotherapy, providing an excellent direction for the development and clinical application of immunotherapeutic strategies for related diseases. This review provides a concise summary of the role of the STING pathway in tumors in recent years.