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Tim-3 in Leukemia; Immune Response and Beyond Publisher



Rezaei M1 ; Tan J2 ; Zeng C3 ; Li Y3 ; Ganjalikhanihakemi M1, 4
Authors
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Authors Affiliations
  1. 1. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China
  3. 3. Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
  4. 4. Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Frontiers in Oncology Published:2021


Abstract

T cell immunoglobulin and mucin domain 3 (TIM-3) expression on malignant cells has been reported in some leukemias. In myelodysplastic syndrome (MDS), increased TIM-3 expression on TH1 cells, regulatory T cells, CD8+ T cells, and hematopoietic stem cells (HSCs), which play a role in the proliferation of blasts and induction of immune escape, has been reported. In AML, several studies have reported overexpression of TIM-3 on leukemia stem cells (LSCs) but not on healthy HSCs. Overexpression of TIM-3 on exhausted CD4+ and CD8+ T cells and leukemic cells in CML, ALL, and CLL patients could be a prognostic risk factor for poor therapeutic response and relapse in patients. Currently, several TIM-3 inhibitors are used in clinical trials for leukemias, and some have shown encouraging response rates for MDS and AML treatment. For AML immunotherapy, blockade TIM-3 may have dual effects: directly inhibiting AML cell proliferation and restoring T cell function. However, blockade of PD-1 and TIM-3 fails to restore the function of exhausted CD8+ T cells in the early clinical stages of CLL, indicating that the effects of TIM-3 blockade may be different in AML and other leukemias. Thus, further studies are required to evaluate the efficacy of TIM-3 inhibitors in different types and stages of leukemia. In this review, we summarize the biological functions of TIM-3 and its contribution as it relates to leukemias. We also discuss the effects of TIM-3 blockade in hematological malignancies and clinical trials of TIM-3 for leukemia therapy. © Copyright © 2021 Rezaei, Tan, Zeng, Li and Ganjalikhani-Hakemi.
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