Targeting TIM-3 in solid tumors: innovations in the preclinical and translational realm and therapeutic potential

Introduction: Immune checkpoint inhibitors (ICIs) have shown a great therapeutic efficacy in cancer patients. However, a significant proportion of cancer patients remain unresponsive or show limited response. T cell immunoglobulin and mucin-domain containing protein-3 (TIM-3) is a co-inhibitory receptor expressed on various cell types and is involved in the attenuation of immune responses. TIM-3 and its ligands are highly expressed in various solid malignancies and some studies have reported its association with worse disease outcomes. Thus, targeting TIM-3 could be a promising therapeutic approach to treat cancer patients. Areas covered: This review describes the role of TIM-3 and its ligands in regulating anti-tumor immunity and their contribution to cancer progression. Moreover, this review focuses on the preclinical models and translational data from important studies published in PubMed till October 2020, which demonstrate the therapeutic benefits of targeting TIM-3 signaling. Expert opinion: Despite the promising data obtained from targeting TIM-3 in preclinical models, precise mechanisms underlying the anti-tumor effects of TIM-3 inhibition are not fully elucidated. Therefore, mechanistic studies are required to provide better insights into the anti-tumor effects of targeting TIM-3, and clinical data are necessary to determine the safety profiles and therapeutic efficacy of TIM-3 inhibition in cancer patients.