ArticleBlood advances2019
PTCy ameliorates GVHD by restoring regulatory and effector T-cell homeostasis in recipients with PD-1 blockade.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Updates from a single-center phase 2 study of PD-1 inhibitor combined with hypomethylating agent plus CAG regimen in patients with relapsed/refractory acute myeloid leukemia.Frontiers in immunology · 2025Trial
- Synergistic venetoclax and anti-CD3 therapy for control of alloreactive response in hematopoietic stem cell transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Immune reconstitution and infections with ATG versus post-transplant cyclophosphamide as GvHD prophylaxis after nonmyeloablative matched unrelated donor hematopoietic stem cell transplantation.Frontiers in immunology · 2026Article
- Low- and high-dose post-transplant cyclophosphamide attenuates graft-versus-host disease with distinct effects on PD-1+ T cell subsets.Clinical science (London, England : 1979) · 2025Article
- Review
- Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHD.The Journal of clinical investigation · 2024Article
- The influence of immune checkpoint blockade on the outcomes of allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2024Review
- Anti-PD-1 combined with hypomethylating agent and CAG regimen bridging to allogeneic hematopoietic stem cell transplantation: a novel strategy for relapsed/refractory acute myeloid leukemia.Frontiers in immunology · 2024Article
- Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD.Blood advances · 2023Article
- Posttransplant cyclophosphamide vs tacrolimus-based GVHD prophylaxis: lower incidence of relapse and chronic GVHD.Blood advances · 2023Article
- Immunopathogenic mechanisms and modulatory approaches to graft-versus-host disease prevention in acute myeloid leukaemia.Best practice & research. Clinical haematology · 2023Review
- Hematopoietic stem cell-derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide.JCI insight · 2023Article
- Checkpoint inhibition in hematologic malignancies.Frontiers in oncology · 2023Review
- High Dose Cyclophosphamide for the Treatment of Severe Immune Checkpoint Inhibitor Related Adverse Events.Journal of oncology research and therapy · 2023Article
- Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant.Journal of hematology & oncology · 2022Article
- Post-transplant cyclophosphamide limits reactive donor T cells and delays the development of graft-versus-host disease in a humanized mouse model.Immunology · 2021Article
- Article
- Use of checkpoint inhibitors in patients with lymphoid malignancies receiving allogeneic cell transplantation: a review.Bone marrow transplantation · 2021Review
- Article
- Impaired T- and NK-cell reconstitution after haploidentical HCT with posttransplant cyclophosphamide.Blood advances · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a significant cause of morbidity and mortality. Regulatory T cells (Tregs) are critical mediators of immune tolerance after allo-HSCT. Clinical studies have indicated that programmed cell death 1 (PD-1) blockade before allo-HSCT involves a risk of severe GVHD. However, the mechanisms underlying GVHD induction resulting from PD-1 blockade remain unclear. We investigated the impact of PD-1 expression of donor T cells on T-cell reconstitution and GVHD using murine models. We first demonstrated that inhibition of PD-1 signaling induced aggressive expansion of CD4+ conventional T cells; however, Tregs could not maintain expansion because of high susceptibility to apoptosis, resulting in discordant immune recovery and subsequent development of severe GVHD. We then evaluated the impact of posttransplantation cyclophosphamide (PTCy) on abnormal T-cell reconstitution after PD-1 blockade. PTCy efficiently ameliorated GVHD after transplantation from a PD-1-/- donor and extended overall survival by safely regulating the proliferation and apoptosis of T-cell subsets. Notably, in the first 2 weeks after administration of PTCy, Tregs regained their ability to continuously proliferate, resulting in well-balanced reconstitution of donor T-cell subsets. In conclusion, the influence of PD-1 blockade differed within T-cell subsets and caused unbalanced reconstitution of T-cell subsets, resulting in severe GVHD. PTCy successfully restored T-cell homeostasis and ameliorated GVHD induced by PD-1-/- donor T cells. These findings may help explain the pathophysiology behind the observation that PTCy may mitigate the incidence and impact of GVHD associated with prior exposure to PD-1 blockade.
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