The intriguing roles of Siglec family members in the tumor microenvironment

Abstract

Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.

Proteomic Discovery of Plasma Protein Biomarkers and Development of Models Predicting Prognosis of High-Grade Serous Ovarian Carcinoma

“…SIGLEC family proteins play diverse immune and nonimmune regulatory roles in the tumor microenvironment and participate in tumor progression. Facilitating tumor immune escape is one of the mechanisms by which tumors progress ( 53 ). Compared with other SGILEC family proteins, the prognostic role of SIGLEC14 in ovarian cancer is not fully understood.…”

Tumor microenvironment signaling and therapeutics in cancer progression

“…The function of inhibitory siglecs closely resembles the PD‐1 immune checkpoint function (Figure 1 ) [ 266 , 267 ]. TME also promotes abnormal sialylation in tumor cells and modulates the expression of siglec on infiltrating immune cells [ 268 ]. Future studies could explore the approach to target the dysregulation of the sialoglycan‐siglec axis in cancer, which could contribute to shaping the immunosuppressive TME, composing an obstacle to overcome towards effective immunotherapy in cancers.…”

Checkpoint Markers and Tumor Microenvironment: What Do We Know?

“…Siglecs: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are transmembrane sialic acid-binding proteins of the immunoglobulin superfamily characterized by the presence of an N-terminal V-set Ig-like domain along with variable numbers of C2 set domains [ 39 ]. Siglecs are of interest in cancer since they have been shown to induce immunosuppression, and as such, attractive as targets for anti-cancer effects.…”