title: A short treatment with galactomannan GM-CT-01 corrects the functions of freshly isolated human tumor-infiltrating lymphocytes.
abstract: OBJECTIVE
  Several galectins are released by tumor cells and macrophages and accumulate in the tumor microenvironment. Galectin-1 and -3 were found to bind to glycosylated receptors at the surface of tumor-infiltrating lymphocytes (TIL), forming glycoprotein-galectin lattices that could reduce the motility and therefore the functionality of surface molecules. In contrast to blood T cells, human TIL show defective IFN-γ secretion upon ex vivo stimulation. We have previously shown that extracellular galectin-3 participates in the impairment of TIL functions. Indeed, disruption of glycoprotein-galectin-3 lattices using anti-galectin-3 antibodies, or N-acetyllactosamine as a competing sugar, boosted cytokine secretion by TIL. Here we have tested a clinical grade galectin antagonist: GM-CT-01, a galactomannan obtained from guar gum reported to be safe in more than 50 patients with cancer.
  
  
  METHODS
  TIL were isolated from human tumor ascites, treated for 2 to 20 hours with galectin antagonists and tested for function.
  
  
  RESULTS
  We found that GM-CT-01 boosts cytotoxicity of CD8(+) TIL and their IFN-γ secretion in a dose-dependent manner. Treating TIL obtained from patients with various cancers, during a few hours, resulted in an increased IFN-γ secretion in up to 80% of the samples.
  
  
  CONCLUSIONS
  These observations pave the way for investigating the potential benefit of this galectin antagonist in patients with cancer, alone or combined with cancer vaccination, in order to correct in vivo impaired functions of TIL.
authors: Authors' Affiliations: Ludwig Institute for Cancer Research Brussels and WELBIO; de Duve Institute; Departments of Gynecology and Oncology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain; Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Medical School of the Vrije Universiteit Brussel, Brussels; and Department of Oncology, Grand Hôpital de Charleroi, Charleroi, Belgium.
authors: Nathalie
authors: N
authors: Demotte
authors: René
authors: R
authors: Bigirimana
authors: Grégoire
authors: G
authors: Wieërs
authors: Vincent
authors: V
authors: Stroobant
authors: Jean-Luc
authors: JL
authors: Squifflet
authors: Javier
authors: J
authors: Carrasco
authors: Kris
authors: K
authors: Thielemans
authors: Jean-François
authors: JF
authors: Baurain
authors: Patrick
authors: P
authors: Van Der Smissen
authors: Pierre J
authors: PJ
authors: Courtoy
authors: Pierre
authors: P
authors: van der Bruggen
mesh_terms: D001798:Blood Proteins; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005690:Galactose / Q000031:analogs & derivatives; D037483:Galectin 1 / Q000378:metabolism; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D037161:Galectins; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008351:Mannans / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
chemical_list: D001798:Blood Proteins; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D008351:Mannans; C012990:galactomannan; D007371:Interferon-gamma; D005690:Galactose