A Galectin-3 Ligand Corrects the Impaired Function of Human CD4 and CD8 Tumor-Infiltrating Lymphocytes and Favors Tumor Rejection in Mice
2010; American Association for Cancer Research; Volume: 70; Issue: 19 Linguagem: Inglês
10.1158/0008-5472.can-10-0761
ISSN1538-7445
AutoresNathalie Demotte, Grégoire Wieërs, Patrick Van Deŕ Smissen, Muriel Moser, Christopher Schmidt, Kris Thielemans, Jean-Luc Squifflet, Birgit Weynand, Javier Carrasco, Christophe Lurquin, Pierre J. Courtoy, Pierre van der Bruggen,
Tópico(s)Signaling Pathways in Disease
ResumoAbstract Human CD8+ tumor-infiltrating T lymphocytes (TIL), in contrast with CD8+ blood cells, show impaired IFN-γ secretion on ex vivo restimulation. We have attributed the impaired IFN-γ secretion to a decreased mobility of T-cell receptors on 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 strengthened 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 on ex vivo restimulation. 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 nonvaccinated 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. Cancer Res; 70(19); 7476–88. ©2010 AACR.
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