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TIM-3 in Leukemia; Immune Response and Beyond.

Mahnaz Rezaei1, Jiaxiong Tan2, Chengwu Zeng3

  • 1Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Frontiers in Oncology
|October 18, 2021
PubMed
Summary

T cell immunoglobulin and mucin domain 3 (TIM-3) is overexpressed in various leukemias, impacting immune escape and prognosis. TIM-3 inhibitors show promise in clinical trials for treating myelodysplastic syndrome and acute myeloid leukemia.

Keywords:
TIM-3acute lymphoblastic leukemiaacute myeloid leukemiachronic lymphoblastic leukemiachronic myeloid leukemiamyelodysplastic syndrome

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Area of Science:

  • Immunology
  • Hematology
  • Oncology

Background:

  • T cell immunoglobulin and mucin domain 3 (TIM-3) expression is observed on malignant cells in several leukemia types.
  • Increased TIM-3 expression on immune cells and hematopoietic stem cells (HSCs) in myelodysplastic syndrome (MDS) contributes to blast proliferation and immune evasion.
  • TIM-3 is overexpressed on leukemia stem cells (LSCs) in acute myeloid leukemia (AML) but not healthy HSCs, and on exhausted T cells in various leukemias, potentially indicating poor prognosis.

Purpose of the Study:

  • To review the biological functions of TIM-3 in relation to leukemias.
  • To discuss the impact of TIM-3 blockade on hematological malignancies.
  • To summarize clinical trials investigating TIM-3 inhibitors for leukemia therapy.

Main Methods:

  • Literature review of studies on TIM-3 expression in leukemias.
  • Analysis of the role of TIM-3 in immune escape and disease progression.
  • Examination of clinical trial data for TIM-3 inhibitors in hematological malignancies.

Main Results:

  • TIM-3 overexpression is linked to poor therapeutic response and relapse risk in leukemias like CML, ALL, and CLL.
  • TIM-3 inhibitors are under investigation, with some showing positive responses in MDS and AML.
  • TIM-3 blockade may inhibit AML proliferation and restore T cell function, but its efficacy varies across leukemia types.

Conclusions:

  • TIM-3 plays a significant role in leukemia pathogenesis and immune regulation.
  • TIM-3 inhibitors represent a potential therapeutic strategy for certain leukemias.
  • Further research is needed to determine the efficacy of TIM-3 blockade in diverse leukemia types and stages.