Galectin-3 and cancer immunotherapy: a glycobiological rationale to overcome tumor immune escape

Abstract

Immunotherapy with checkpoint inhibitors (ICIs) has radically changed the landscape of therapeutic opportunities in oncology, but much still needs to be understood from a mechanistic point of view. There is space for further improving tumors’ response to ICIs, as supported by a strong biological rationale. For this achievement a detailed analysis of tumor cell phenotype with functional dissection of the molecular interactions occurring in the TME is required. Galectin-3 is a pleiotropic tumor relevant molecule, which deserves particular attention in immuno-oncology. Due to its ability to finely modulate immune response in vivo, Galectin-3 is a potential target molecule to be considered for overcoming tumor immune escape.

Do galectins serve as soluble ligands for immune checkpoint receptors?

“…35 36 These results highlight the importance of galectin-3 as an emerging target of cancer immunotherapy either alone or in different combination modalities. [34][35][36][37] Like galectin-3 and galectin-9, galectin-1 has been shown to shape antitumor immune responses and foster immunosuppressive networks through modulation of lymphoid and myeloid cells. 3 These effects include induction of apoptosis of Th1, Th17 and CD8 + T cells, expansion of CD4 + and CD8 + regulatory T cells and promotion of tolerogenic dendritic cells and immunosuppressive tumor-associated macrophages.…”