Exploring CD169⁺ Macrophages as Key Targets for Vaccination and Therapeutic Interventions

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that is expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well as glycolipids present on the surface of immune cells and pathogens. CD169-expressing macrophages exert tissue-specific homeostatic functions, but they also have opposing effects on the immune response. CD169⁺ macrophages act as a pathogen filter, protect against infectious diseases, and enhance adaptive immunity, but at the same time pathogens also exploit them to enable further dissemination. In cancer, CD169⁺ macrophages in tumor-draining lymph nodes are correlated with better clinical outcomes. In inflammatory diseases, CD169 expression is upregulated on monocytes and on monocyte-derived macrophages and this correlates with the disease state. Given their role in promoting adaptive immunity, CD169⁺ macrophages are currently investigated as targets for vaccination strategies against cancer. In this review, we describe the studies investigating the importance of CD169 and CD169⁺ macrophages in several disease settings and the vaccination strategies currently under investigation.