title: A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion.
abstract: Surface galectin has been shown to contribute to dysfunctions of human tumour-infiltrating lymphocytes (TILs). We show here that galectin-covered CD8 TILs produce normal amounts of intracellular cytokines, but fail to secrete them because of defective actin rearrangements at the synapse. The non-secreting TILs also display reduced adhesion to their targets, together with defective LFA-1 recruitment and activation at the synapse. These defects are relieved by releasing surface galectin. As mild LFA-1 blockade on normal blood T cells emulate the defects of galectin-covered TILs, we conclude that galectin prevents the formation of a functional secretory synapse by preventing optimal LFA-1 triggering. Our results highlight a major secretory defect of TILs that is not revealed by widely used intracellular cytokine immunomonitoring assays. They also provide additional insights into the T-cell response, by showing that different thresholds of LFA-1 triggering are required to promote the intracellular production of cytokines and their secretion.
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Anne-Elisabeth
authors.initials: AE
authors.lastname: Petit
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Demotte
authors.affiliation: TIPs, Université Libre de Bruxelles, B-1050 Brussels, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Scheid
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Wildmann
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: René
authors.initials: R
authors.lastname: Bigirimana
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Monica
authors.initials: M
authors.lastname: Gordon-Alonso
authors.affiliation: Department of Oncology, Grand Hôpital de Charleroi, B-6000 Charleroi, Belgium.
authors.forename: Javier
authors.initials: J
authors.lastname: Carrasco
authors.affiliation: INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan, F-31024 Toulouse, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Danièle
authors.initials: D
authors.lastname: Godelaine
authors.affiliation: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
mesh_terms: D000606:Amino Sugars; D002448:Cell Adhesion; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D037161:Galectins; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: D000606:Amino Sugars; D016207:Cytokines; D037161:Galectins; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; C000458:N-acetyllactosamine