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

ABSTRACT

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.

KEYWORDS:

• Cancer
• TIM-3
• solid tumors
• prognostic biomarker
• therapeutic target

Article highlights

• Despite the success of anti-PD-1/anti-PD-L1 and anti-CTLA-4 in treating various solid tumors, there are some patients who are refractory to these therapies.

• TIM-3 is a co-inhibitory immune checkpoint receptor and could be upregulated in response to anti-PD-1/PD-L1 or anti-CTLA-4 therapy, resulting in acquired resistance.

• TIM-3 and its ligands can be expressed by various immune cell types and tumor cells.

• TIM-3 could serve as a prognostic biomarker for many solid tumors.

• Inhibition of TIM-3 signaling in preclinical models positively regulates innate and adaptive immunity and alleviates T cell exhaustion in various disease contexts, including cancer and chronic infections.

• Inhibition of TIM-3 could further advance the landscape of immunotherapy for treating solid tumors.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.