One Stone, Two Birds: The Roles of Tim-3 in Acute Myeloid Leukemia

Zhiding Wang,Li Yu,Mengzhen Wang,Jinghong Chen,Linlin Zhang

doi:10.3389/fimmu.2021.618710

Abstract

T cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint and plays a vital role in immune responses during acute myeloid leukemia (AML). Targeting Tim-3 kills two birds with one stone by balancing the immune system and eliminating leukemia stem cells (LSCs) in AML. These functions make Tim-3 a potential target for curing AML. This review mainly discusses the roles of Tim-3 in the immune system in AML and as an AML LSC marker, which sheds new light on the role of Tim-3 in AML immunotherapy.

Highlights

T cell immunoglobulin and mucin protein 3 (Tim-3) was first discovered in 2002 and is a type I membrane-bound glycoprotein [1]
Cytotoxic lymphoid cells in acute myeloid leukemia (AML) could be suppressed from a distance by AML cells after the formation of a Tim-3 and galectin 9 (Gal-9) autocrine loop
Stem cell factor (SCF) is a key cytokine that contributes to the development of AML, and it is important to understand the mechanism underlying the interactions of Tim-3-mediated responses with SCF-induced signaling networks [44,45,46]

Summary

INTRODUCTION

T cell immunoglobulin and mucin protein 3 (Tim-3) was first discovered in 2002 and is a type I membrane-bound glycoprotein [1]. Multiple lines of evidence highlight the role of the Tim-3/Gal-9 interaction in mediating the inhibition of immune responses in different cell types [9]. The Gal-9/Tim-3 interaction is capable of activating downstream signaling pathways such as the transcription factor NF-kB [40] to support the survival of AML cells. Cytotoxic lymphoid cells in AML could be suppressed from a distance by AML cells after the formation of a Tim-3 and Gal-9 autocrine loop This indirect interaction could contribute to AML cell self-renewal, resulting in the rapid development of AML [25]. Stem cell factor (SCF) is a key cytokine that contributes to the development of AML, and it is important to understand the mechanism underlying the interactions of Tim-3-mediated responses with SCF-induced signaling networks [44,45,46]. The potential therapeutic function and mechanism of Tim-3 in LSCs in AML remain to be explored

Preclinical Research

Clinical Research

Findings

FUTURE PERSPECTIVES