[Is it possible to correct the anergy of T lymphocytes that infiltrate tumors?].
Human tumor metastases are often infiltrated by T lymphocytes that are specific for tumor antigens, but these metastases progress anyway. The spontaneous anti-tumor immune response seems thus to become ineffective, probably because the effector T cells become anergic. This anergy could result from inhibitory mechanisms orchestrated by the tumor cells. We have observed that recently stimulated human cytolytic T cell clones lose transiently their capacity to secrete cytokines. This anergy is correlated with the absence of colocalization of the T cell receptors (TCR) and the CD8 co-receptors. Effector functions' and TCR/CD8 colocalization are recovered by treating cells with galectin-3 ligands, suggesting that exracellular galectin-3 forms glycoprotein-galectin lattices, which decrease the TCR mobility on the surface of anergic T lymphocytes. Galectin-3 is frequently released by tumor cells. This new mechanism of anergy could thus also explain the loss of functions of the tumor-infiltrating lymphocytes, because these lymphocytes recover their effector functions and TCR/CD8 colocalization after ex vivo treatment with galectin-3 ligands. These results could lead to new therapeutical strategies.
van der Bruggen
P
P
Ludwig Institute for Cancer Research.
D017635:Clonal Anergy / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology
D016207:Cytokines