Author(s): Nathalie Demotte, Grgoire Wiers, Patrick Van Der Smissen, Muriel Moser, Christopher W Schmidt, Kris Thielemans, JeanLuc Squifflet, Birgit Weynand, Javier Carrasco, Christophe Lurquin, Pierre J Courtoy, Pierre van der Bruggen
Human CD8+ tumor-infiltrating T lymphocytes (TIL), in contrast with CD8+ blood cells, show impaired IFN-γ secretion upon ex vivo re-stimulation. We have attributed the impaired IFN-γ secretion to a decreased mobility of T cell receptors upon trapping in a lattice of glycoproteins clustered by extracellular galectin-3. Indeed, we have previously shown that treatment with N-acetyllactosamine, a galectin ligand, restored this secretion. We strenghtened this hypothesis here by showing that CD8+ TIL treated with an anti-galectin-3 antibody had an increased IFN-γ secretion. Moreover, we found that GCS-100, a polysaccharide in clinical development, detached galectin-3 from TIL and boosted cytotoxicity and secretion of different cytokines. Importantly, we observed that not only CD8+ TIL but also CD4+ TIL treated with GCS-100 secreted more IFN-γ upon ex vivo re-stimulation. In tumor-bearing mice vaccinated with a tumor antigen, injections of GCS-100 led to tumor rejection in half of the mice, whereas all control mice died. In non-vaccinated mice, GCS-100 had no effect by itself. These results suggest that a combination of galectin-3 ligands and therapeutic vaccination may induce more tumor regressions in cancer patients than vaccination alone.