A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion

Anne-Elisabeth Petit, Nathalie Demotte, Benoît Scheid, Claude Wildmann, René Bigirimana, Monica Gordon-Alonso, Javier Carrasco, Salvatore Valitutti, Danièle Godelaine and Pierre van der Bruggen ()
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Anne-Elisabeth Petit: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
Nathalie Demotte: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
Benoît Scheid: TIPs, Université Libre de Bruxelles
Claude Wildmann: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
René Bigirimana: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
Monica Gordon-Alonso: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
Javier Carrasco: Grand Hôpital de Charleroi
Salvatore Valitutti: INSERM, UMR 1043, Centre de Physiopathologie de Toulouse Purpan
Danièle Godelaine: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain
Pierre van der Bruggen: Ludwig Institute for Cancer Research, WELBIO and de Duve Institute, Université catholique de Louvain

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12242

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