The impact of regulatory T cells on the graft-versus-leukemia effect

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only curative therapy for many hematologic malignancies, whereby the Graft-versus-Leukemia (GVL) effect plays a pivotal role in controlling relapse. However, the success of GVL is hindered by Graft-versus-Host Disease (GVHD), wher...

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Bibliographic Details
Published in:Frontiers in immunology 2024-04, Vol.15, p.1339318-1339318
Main Authors: Pacini, Carolina P, Soares, Maria V D, Lacerda, João F
Format: Article
Language:English
Subjects:
Adoptive Transfer - methods
Animals
cell therapy
Graft vs Host Disease - immunology
Graft vs Host Disease - prevention & control
Graft vs Leukemia Effect - immunology
graft-versus-leukemia
GvHD
Hematologic Neoplasms - immunology
Hematologic Neoplasms - therapy
Hematopoietic Stem Cell Transplantation
Humans
Immunology
immunomodulation
regulatory T cell
T-Lymphocytes, Regulatory - immunology
Transplantation, Homologous
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Summary:Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is the only curative therapy for many hematologic malignancies, whereby the Graft-versus-Leukemia (GVL) effect plays a pivotal role in controlling relapse. However, the success of GVL is hindered by Graft-versus-Host Disease (GVHD), where donor T cells attack healthy tissues in the recipient. The ability of natural regulatory T cells (Treg) to suppress immune responses has been exploited as a therapeutical option against GVHD. Still, it is crucial to evaluate if the ability of Treg to suppress GVHD does not compromise the benefits of GVL. Initial studies in animal models suggest that Treg can attenuate GVHD while preserving GVL, but results vary according to tumor type. Human trials using Treg as GVHD prophylaxis or treatment show promising results, emphasizing the importance of infusion timing and Treg/Tcon ratios. In this review, we discuss strategies that can be used aiming to enhance GVL post-Treg infusion and the proposed mechanisms for the maintenance of the GVL effect upon the adoptive Treg transfer. In order to optimize the therapeutic outcomes of Treg administration in allo-HSCT, future efforts should focus on refining Treg sources for infusion and evaluating their specificity for antigens mediating GVHD while preserving GVL responses.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1339318