Innate immune cell lectins (CLRs/Siglecs)

Innate immune cell lectins represent a broad class of carbohydrate-binding receptors expressed on macrophages, neutrophils, and natural killer (NK) cells that facilitate the recognition of self and non-self glycans. This group primarily includes C-type lectin receptors (CLRs) like Dectin-1 and Mincle, as well as Sialic acid-binding immunoglobulin-type lectins (Siglecs) and Galectins. These receptors function as pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) on fungi, bacteria, and viruses, or damage-associated molecular patterns (DAMPs) on stressed or malignant cells (Geijtenbeek & Gringhuis, 2009; Nat Rev Immunol). In the context of oncology, many of these lectins act as glyco-immune checkpoints; for instance, Siglec-7 and Siglec-9 on NK cells and macrophages provide inhibitory signals when they bind to hypersialylated tumor cells, effectively dampening the anti-tumor immune response (Duan & Paulson, 2020; Annu Rev Immunol). Conversely, activating lectins like NKG2D and Dectin-1 can be targeted to stimulate innate immunity against infections and cancer. Therapeutic development in this space involves monoclonal antibodies that block inhibitory lectin signaling, such as Monalizumab targeting NKG2A, or glycan-modifying agents like sialidases that strip the protective glycan shield from tumors (Palleon Pharmaceuticals, 2023). Understanding the complex 'glyco-code' of these receptors is essential for developing next-generation immunotherapies that bridge innate and adaptive immunity.

Other names

C-type lectin receptorsSialic acid-binding immunoglobulin-type lectinsCarbohydrate-binding proteinsPattern recognition receptorsGlyco-immune checkpointsLectins on myeloid and NK cells

Modulation of immune checkpoint signaling, enhancement of phagocytic activity, induction of pro-inflammatory cytokine release, and desialylation of the tumor microenvironment.