Siglec15 in blood system diseases: from bench to bedside

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• The PD-1/PD-L1 pathway is a validated target in cancer immunotherapy.
• Sialic acid-binding immunoglobulin-like lectin (Siglec-15) is a newly identified inhibitory immune checkpoint.
• Siglec-15 is highly expressed in various solid tumors and tumor-associated macrophages, and is upregulated across cancer types.

Purpose of the Study:

• To review the biological attributes, expression patterns, and pathogenic mechanisms of Siglec-15 in various diseases.
• To evaluate the role of Siglec-15 in the pathogenesis and laboratory diagnosis of hematological disorders.
• To highlight Siglec-15 as a potential target for next-generation cancer immunotherapies.

Main Methods:

• Literature review of biological attributes, expression patterns, and pathogenic mechanisms of Siglec-15.
• Evaluation of Siglec-15's role in disease pathogenesis and diagnosis.
• Analysis of Siglec-15's potential as a therapeutic target.

Main Results:

• Siglec-15 plays a role in immune evasion, particularly in PD-L1-negative cancers.
• Siglec-15 represses T lymphocyte activation and proliferation, promoting tumor immune escape.
• Siglec-15 is implicated in osteoclast differentiation and bone remodeling.
• Siglec-15 expression in tumor cells may offer a novel therapeutic strategy for hematological malignancies.

Conclusions:

• Siglec-15 represents a promising target for novel cancer immunotherapies, especially for hematological malignancies.
• Understanding Siglec-15's role is crucial for developing effective treatments for immune evasion and bone remodeling-related pathologies.
• Targeting Siglec-15 could overcome resistance to existing immunotherapies and address unmet needs in cancer treatment.