STING expression in colorectal cancer: prognostic role and immune microenvironment link via mIHC

Colorectal cancer (CRC) is a malignant tumor originating in the mucosal epithelium of the colon or rectum and is among the most common cancers of the digestive system. Now it is the fourth deadliest cancer in the world. Stimulator of Interferon Genes (STING) is a dimeric transmembrane protein on the endoplasmic reticulum membrane that induces the secretion of type I interferons and pro-inflammatory cytokines and is triggered by the cell membrane DNA of pathogens and hosts. It is widely expressed in immune cells (such as dendritic cells, macrophages) and some tumor cells, and has been shown to play a crucial role in the development of several tumors. However, issues such as the expression of STING in CRC and patient prognosis remain to be further elucidated. We investigated the expression of STING (in CRC tumor cells) and immune markers (CD3, CD4, CD8, CD56, CD163) in 86 CRC patients by tissue microarray using multicolor immunohistochemistry. Subsequently, the effect of STING on the tumor immune microenvironment was further explored. Finally, we analyzed the clinical significance of STING in CRC patients. We found elevated STING expression in tumor cells from CRC patients, which correlated with overall patient survival. High STING levels were associated with suppression of lymph node metastasis and reduction of CD163 tumor-associated macrophages. In contrast, upregulation of STING promoted infiltration of CD3+ T lymphocytes and CD8 lymphocyte subtype in the tumor microenvironment. Our study demonstrated that changes in STING expression in cancer cells in the tumor immune microenvironment have clinical significance and regulatory roles. STING-related functional mechanisms can be considered as therapeutic targets for CRC, which provides a theoretical basis for the subsequent clinical application of STING agonists.