{"doi":"10.3390/ijms26167998","title":"Galectin-9—An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy","abstract":") is a member of the family of carbohydrate-binding lectins known as galectins. Galectins bind a diverse repertoire of galactose-bearing glycoprotein receptors expressed across multiple cell types. These interactions elicit a broad spectrum of pleiotropic effects important in both normal physiology and disease pathogenesis. Gal-9 contains two separate carbohydrate recognition domains with overlapping yet also divergent binding affinities for distinct glycostructures. This tandem repeat motif enables fine-tuning of its various biological functions. Additional control of Gal-9 activity is provided via multiple gene variants, protein isoforms, tissue distribution, and cell type-associated glycoprotein binding profiles. Within the tumor microenvironment, Gal-9 interacts with immune, non-immune, and cancer cells to influence malignant progression. Its binding of the premier immune checkpoint glycoreceptors, T-cell immunoglobulin and mucin-domain-containing-3 (TIM-3) and programmed cell death protein 1 (PD-1), places Gal-9 apart as a burgeoning target for immunotherapy. In this review, we delve into important aspects of Gal-9 immunobiology in tumorigenesis, including glycobiological and lineage-dependent functions. We further examine Gal-9 as a promising new glyco-immune checkpoint target for cancer therapy.","journal":"International Journal of Molecular Sciences","year":2025,"id":512233,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":892921,"name":"Tobias Schatton","orcid":"0000-0003-1386-680X","position":1,"is_corresponding":false},{"id":892931,"name":"Steven R. Barthel","orcid":"0000-0003-2107-4570","position":2,"is_corresponding":false},{"id":1212899,"name":"Anastasia Iris Karkempetzaki","orcid":null,"position":0,"is_corresponding":true}],"reference_count":257,"raw_metadata":null,"created_at":"2026-07-19T02:48:06.263458Z","pmid":"40869319","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}