The role of T-cell immunoglobulin mucin-3 and its ligand galectin-9 in antitumor immunity and cancer immunotherapy

Cancer treatment in the past few years has been transformed by a new kind of therapy that targets the immune system instead of the cancer itself to reinvigorate antitumor immunity with astonishing results. However, primary and acquired resistance to this type of treatment, namely immune checkpoint blockade (ICB), continue to counter treatment efficacy. In many cases, resistance has been attributed to defective or chronically enhanced interferon signaling and/or upregulation of alternative immune checkpoints, including T-cell immunoglobulin mucin-3 (Tim-3) and its ligand galactin-9 (Gal-9). In this article, we briefly describe the current knowledge of common checkpoint resistance mechanisms, focusing on the Tim-3/Gal-9 pathway as an alternative checkpoint that holds great promise as another target for ICB.