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

作者：Petit Anne Elisabeth; Demotte Nathalie; Scheid Benoit; Wildmann Claude; Bigirimana Rene; Gordon Alonso Monica; Carrasco Javier; Valitutti Salvatore; Godelaine Daniele; van der Bruggen Pierre^*

来源：Nature Communications, 2016, 7(1): 12242.

DOI：10.1038/ncomms12242

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.

• 出版日期2016-7