ArticleThe Journal of clinical investigation2010
Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 95 citations in OpenAlex.
- Prognostic values of increased B7 family proteins in haploidentical hematopoietic stem cell transplantation patients with aGVHD.International journal of hematology · 2019Trial
- Minor histocompatibility antigen TCR-T.Blood advances · 2026Review
- Recent advances in the pathophysiology of acute and chronic graft-versus-host disease.International journal of hematology · 2026Review
- Novel approaches for separating graft-versus-leukemia effects from graft-versus-host disease.Frontiers in oncology · 2026Review
- PD-1 inhibition for relapse after allogeneic transplantation in acute myeloid leukemia and myelodysplastic syndrome.Blood advances · 2025Article
- Pembrolizumab-Induced Severe Pneumonitis in a Patient With Lung Adenocarcinoma After Umbilical Cord Blood Transplantation: A Case Report.Respirology case reports · 2025Article
- IFN-γ and donor leukocyte infusions for relapsed myeloblastic malignancies after allogeneic hematopoietic stem cell transplantation.JCI insight · 2025Article
- Chemokine receptors are required for effector T-cell trafficking to GVHD tissues but not to bone marrow.Blood advances · 2025Article
- Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.Biomarker research · 2024Review
- Article
- Transcription factor KLF2 is associated with the dysfunctional status of NK cells and the prognosis of pediatric B-ALL patients.Frontiers in oncology · 2024Article
- Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML.Blood advances · 2023Article
- Graft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells.Immunity · 2023Article
- Separation of GVL from GVHD -location, location, location.Frontiers in immunology · 2023Review
- Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2022Article
- Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma with HTLV-1-associated myelopathy.International journal of hematology · 2021Article
- The Role of Immune Checkpoint Molecules for Relapse After Allogeneic Hematopoietic Cell Transplantation.Frontiers in immunology · 2021Review
- Baseline immune dysregulation in autologous stem cell transplant recipients is associated with a 'graft versus host'-like syndrome and poor outcomes.Bone marrow transplantation · 2020Article
- T cell exhaustion and a failure in antigen presentation drive resistance to the graft-versus-leukemia effect.Nature communications · 2020Article
- Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD.Nature reviews. Clinical oncology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is used effectively to treat a number of hematological malignancies. Its beneficial effects rely on donor-derived T cell-targeted leukemic cells, the so-called graft-versus-leukemia (GVL) effect. Induction of GVL is usually associated with concomitant development of graft-versus-host disease (GVHD), a major complication of allogeneic HSCT. The T cells that mediate GVL and GVHD are activated by alloantigen presented on host antigen-presenting cells of hematopoietic origin, and it is not well understood how alloantigen expression on non-hematopoietic cells affects GVL activity. Here we show, in mouse models of MHC-matched, minor histocompatibility antigen-mismatched bone marrow transplantation, that alloantigen expression on host epithelium drives donor T cells into apoptosis and dysfunction during GVHD, resulting in a loss of GVL activity. During GVHD, programmed death-1 (PD-1) and PD ligand-1 (PD-L1), molecules implicated in inducing T cell exhaustion, were upregulated on activated T cells and the target tissue, respectively, suggesting that the T cell defects driven by host epithelial alloantigen expression might be mediated by the PD-1/PD-L1 pathway. Consistent with this, blockade of PD-1/PD-L1 interactions partially restored T cell effector functions and improved GVL. These results elucidate a previously unrecognized significance of alloantigen expression on non-hematopoietic cells in GVL and suggest that separation of GVL from GVHD for more effective HSCT may be possible in human patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.