Tumour-reactive B cells and antibody responses after allogeneic haematopoietic cell transplantation

Jong, Greta de; Gillissen, Marijn A.; Spits, Hergen; Hazenberg, Mette D.

doi:10.1016/j.iotech.2020.07.002

Cited by 3 publications

(4 citation statements)

References 87 publications

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“…We also found that B-cell reconstitution was associated with lower risk of relapse. This may be explained by the involvement of B cells in graft-versusleukemia effect and antitumor immunity after allo-HSCT [54][55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

The dynamics of B‐cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real‐world study

Zhou,

Zhan,

Huang

et al. 2024

J Intern Med

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BackgroundThe immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is crucial for preventing infections and relapse and enhancing graft‐versus‐tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo‐HSCT has not been well studied.MethodsIn this study, we analyzed the dynamics of B cells in 252 patients who underwent allo‐HSCT for 2 years and assessed the impact of factors on B‐cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood.ResultsWe found that the B‐cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B‐cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft‐versus‐host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post‐1‐year B‐cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age‐B cells‐survival axis and found that B‐cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037).ConclusionOur findings provide valuable insights for optimizing the management of B‐cell reconstitution and improving the efficacy and safety of allo‐HSCT.

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Section: Discussionmentioning

confidence: 99%

The dynamics of B‐cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real‐world study

Zhou,

Zhan,

Huang

et al. 2024

J Intern Med

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“…This may have relevance beyond solid organ transplantation, most immediately in mixed chimeric states that typically develop following after reduced intensity conditioning and hematopoietic stem cell transplantation for hematological malignancies. The co-existence of donor and recipient lymphocyte fractions may promote spontaneous humoral immunity; indeed, isolated reports describe the generation of anti-tumor antibodies associated with hematopoietic mixed chimerism (8).…”

Section: What Is the Clinical Relevance Of Inverted Direct Allorecogn...mentioning

confidence: 99%

Passenger donor lymphocytes: To affinity and beyond

2022

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“…It is thought that the GVL effect is mediated predominantly by T cells but can also be mediated by natural killer (NK) cells and B cells, and cytokines produced by these cells. 2,7,8 The pathogenesis of GVHD is also mediated predominantly by T cells. As such, one therapeutic strategy for GVHD prevention is the use of post-transplant cyclophosphamide (PTCy), a cytotoxic compound often administered at 50 mg kg À1 on days 3 and 4 post-donor HSCT.…”

Section: Introductionmentioning

confidence: 99%

“…The GVL effect was first observed over 60 years ago, 6 yet despite years of preclinical and clinical studies, the precise mechanism required to achieve GVL immunity without promoting GVHD has not been uncovered. It is thought that the GVL effect is mediated predominantly by T cells but can also be mediated by natural killer (NK) cells and B cells, and cytokines produced by these cells 2,7,8 . The pathogenesis of GVHD is also mediated predominantly by T cells.…”

Section: Introductionmentioning

confidence: 99%

Graft‐versus‐leukaemia immunity is retained following treatment with post‐transplant cyclophosphamide alone or combined with tocilizumab in humanised mice

Sligar,

Reilly,

Cuthbertson

et al. 2024

Clin & Trans Imm

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ObjectivesDonor haematopoietic stem cell transplantation treats leukaemia by inducing graft‐versus‐leukaemia (GVL) immunity. However, this benefit is often mitigated by graft‐versus‐host disease (GVHD), which is reduced by post‐transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity.MethodsNOD‐scid‐IL2Rγnull mice were injected with 2 × 107 human peripheral blood mononuclear cells (hPBMCs) on day 0 and with 1 × 106 THP‐1 acute myeloid leukaemia cells on day 14. In subsequent experiments, mice were also injected with PTCy (33 mg kg−1) or Dulbecco's phosphate buffered saline (PBS) on days 3 and 4, alone or combined with TOC or control antibody (25 mg kg−1) twice weekly for 28 days. Clinical signs of disease were monitored until day 42.ResultsMice with hPBMCs from three different donors and THP‐1 cells showed similar survival, clinical score and weight loss. hCD33+ leukaemia cells were minimal in mice reconstituted with hPBMCs from two donors but present in mice with hPBMCs from a third donor, suggesting donor‐specific GVL responses. hPBMC‐injected mice treated with PTCy alone or combined with TOC (PTCy + TOC) demonstrated prolonged survival compared to control mice. PTCy alone and PTCy + TOC‐treated mice with hPBMCs showed minimal hepatic hCD33+ leukaemia cells, indicating sustained GVL immunity. Further, the combination of PTCy + TOC reduced histological damage in the lung and liver.ConclusionCollectively, this research demonstrates that PTCy alone or combined with TOC impairs GVHD without compromising GVL immunity.

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Tumour-reactive B cells and antibody responses after allogeneic haematopoietic cell transplantation

Cited by 3 publications

References 87 publications

The dynamics of B‐cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real‐world study

The dynamics of B‐cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real‐world study

Passenger donor lymphocytes: To affinity and beyond

Graft‐versus‐leukaemia immunity is retained following treatment with post‐transplant cyclophosphamide alone or combined with tocilizumab in humanised mice

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