Elevated TIM3 expression on bone marrow T cells drives immune dysfunction in early relapsed blood cancer after allogeneic hematopoietic stem cell transplantation

Elevated TIM3 expression on bone marrow T cells drives immune dysfunction in early relapsed blood cancer after allogeneic hematopoietic stem cell transplantation

Abstract Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in patients with hematologic malignancies. To better understand the mechanisms underlying early relapse (ER), we comprehensively explored the expression of inhibitory...

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Main Authors: Thi Thuy Duong Pham, Su-Young Choi, Jeong Suk Koh, Bu-Yeon Heo, Sang-Woo Lee, Myung-Won Lee, Wonhyoung Seo, Yunseon Jang, Jung-Hyun Park, Deog-Yeon Jo, Seungyeul Yoo, Jaeyul Kwon, Ik-Chan Song
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Experimental Hematology & Oncology
Subjects:
T cell immunoglobulin and mucin domain 3 (TIM3)
Inhibitor receptors
Allogeneic hematologic stem cell transplantation (HSCT)
Early relapse (ER)
Double negative t cells (DNTs)
Regulatory t cells (Treg)
Online Access:https://doi.org/10.1186/s40164-025-00697-6
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Summary:Abstract Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in patients with hematologic malignancies. To better understand the mechanisms underlying early relapse (ER), we comprehensively explored the expression of inhibitory receptors (IRs) in bone marrow (BM) T cells at differentiation stage and examined transcriptional differences. Among the evaluated IRs, TIM3 was significantly upregulated in CD3+T cells of patients with ER compared to patients with complete remission (CR). Notably, double-negative T (DNT) cells, a unique subset with MHC-independent cytotoxic potential, constituted a high proportion of BM T cells and expressed increased TIM3 expression in ER patients. Moreover, regulatory T cells (Tregs) showed elevated TIM3 levels, contributing to an immunosuppressive microenvironment after allo-HSCT. Transcriptomic analysis revealed downregulation of cytotoxic granules and effector genes in DNT cells from ER patients. Functional assays demonstrated that TIM3 blockade with sabatolimab restored T cell cytotoxicity, leading to enhanced leukemia cell apoptosis in ER patients. These findings highlight TIM3 as a critical regulator of T cell exhaustion and immune suppression in patients with ER and provide a rationale for the therapeutic use of TIM3 blockade in preventing and treating relapses after allo-HSCT.
ISSN:2162-3619

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