The dual role of lectins in cancer-immunotherapy tools and therapeutic targets.

Altered glycosylation is a hallmark of cancer that shapes immune recognition within the tumor microenvironment. Lectins-glycan-binding proteins-play a dual role in this process: they interpret tumor-associated glycan patterns and can also be exploited as therapeutic tools. In this review, we discuss emerging strategies that harness lectins in cancer immunotherapy. Engineered lectin-based constructs, including antibody-lectin chimeras, lectin-drug conjugates, and glycan-targeting CAR-T cells, enable recognition of tumor-specific glycosylation signatures. At the same time, endogenous lectin pathways such as the galectin-polyLacNAc and sialic acid-Siglec axes function as glyco-immune checkpoints that suppress anti-tumor responses and represent promising therapeutic targets. Understanding how lectins regulate tumor-immune interactions may guide the development of next-generation immunotherapies integrating antigen recognition with glycan sensing.