Zhongguo aizheng zazhi (Dec 2022)
Research progress and prospect of Siglec in innate immune cells in tumor
Abstract
Immunotherapy brings hope to those patients suffering from malignant tumor. However, common immunotherapy targets, such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death ligand-1 (PD-L1), have low positive expression rate in patients, and only a few patients can benefit from immunotherapy. Therefore, finding new immunotherapy targets is extremely important for improving the response rate and effect of immunotherapy. Recent studies have suggested that sialic acid-binding immunoglobulin-type lectin (Siglec) family members are abundantly expressed in innate immune cells, such as macrophages, natural killer (NK) cells and dendritic cells (DC), and are shown to be related to the development of tumors. Different Siglecs play different roles in macrophages, and Siglec-1 enhances the antigen presentation of macrophages and thus the killing effect of CD8+ T cells. Siglec-7 and Siglec-9 induce the differentiation of tumor-associated macrophages (TAM) to immunosuppressive TAM thus affecting the immune microenvironment. Siglec-10 interacts with CD24 to protect tumor cells from macrophage attack, and Siglec-15 also exhibits PD-L1-like related effects, which suggests that it may be a novel immune checkpoint. Siglec-7 and Siglec-9 are highly expressed in NK cells, and these Siglecs exhibit immunosuppressive effects by eliminating cis interactions on the surface of NK cells. The highly expressed sialic acid glycoprotein on the tumor surface would bind to Siglecs on the NK cell surface thereby inhibiting the killing effect of NK cells, and the killing effect of NK cells could be enhanced by eliminating sialic acid on the tumor surface. A proposal to enhance NK cell killing by constructing high-affinity cis-ligands revealed that the concentration of cis-ligands had a very different effect on NK cell killing, suggesting that there is a dynamic balance of sialic acid that affects immune reaction. Siglec-3 and Siglec-9 on the surface of DC bind to tumor mucin, inducing DC apoptosis and reducing the production of immune-related molecules, thereby causing immune escape. The related Siglec has been shown to affect the expression of antigen presentation and immune-related factors in DC in mouse experiments. In this review, we summarized the recent studies of Siglecs in the innate immune system on how they interact with tumors and affecting tumor development, and discussed the potential of them as novel targets for immunotherapy.
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