Significance of TIM3 expression in cancer: From biology to the clinic

Targeting inhibitory immune checkpoint molecules has dramatically changed treatment paradigms in medical oncology. Understanding the best strategies to unleash a pre-existing immune response or to induce an efficient immune response against tumors has emerged as a research priority. In this work, we focus on a novel target for cancer immunotherapy, the inhibitory receptor T-cell immunoglobulin and mucin domain 3 (TIM3). This narrative review describes TIM3 biology in different (tumor-infiltrating) immune cells, particularly in the immunosuppressive regulatory T cells and dysfunctional/exhausted cytotoxic T lymphocytes, but also in cells that confer innate immunity - natural killer and dendritic cells. We discuss the functional role of TIM3, its expression and its clinical significance in a variety of tumors, and confront the heterogeneous results emerging from different studies, including clinical trials of immunotherapy. Finally, this work summarizes the principal early-phase clinical trials exploring TIM3 blockade and discusses some future perspectives. (C) 2019 Elsevier Inc. All rights reserved.