Journal
LEUKEMIA
Volume 34, Issue 12, Pages 3420-3425Publisher
SPRINGERNATURE
DOI: 10.1038/s41375-020-0851-8
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Funding
- Instituto de Salud Carlos III Fondo de Investigaciones Sanitarias [FIS16/01433, PI17/00950, PI17/00943]
- European Regional Development Fund (ERDF)
- Generalitat de Catalunya [BDNS357800]
- Asociacion Espanola Contra el Cancer (Ideas Semilla 2019)
- Ministerio de Ciencia, Innovacion y Universidades [RYC-2012-12018]
- Gilead Fellowships [GLD16/00144, GLD18/00047]
- Asociacion Espanola Contra el Cancer [LABAE18014CRES]
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Patients receiving an allogeneic hematopoietic cell transplantation (allo-HCT) after the use of PD-1 inhibitors seem to be at a higher risk of developing acute graft-versus-host disease (aGHVD) through etiopathogenetic mechanisms not fully elucidated. Herein, we investigated the effect of nivolumab administered prior to allo-HCT on the following early T-cell reconstitution and its modulation by the GVHD prophylaxis (tacrolimus/sirolimus vs. posttransplant cyclophosphamide [PTCY]). In all nivolumab-exposed patients we detected circulating nivolumab in plasma for up to 56 days after allo-HCT. This residual nivolumab was able to bind and block PD-1 on T-cells at day 21 after allo-HCT, inducing a T cell activation that was differentially modulated depending on the GVHD prophylactic regimen. Among patients receiving tacrolimus/sirolimus, nivolumab-exposed patients had a higher incidence of severe aGVHD and a more effector T-cell profile compared with anti-PD-1-naive patients. Conversely, patients receiving PTCY-based prophylaxis showed a similar risk of aGVHD and T-cell profile irrespective of the previous nivolumab exposure. In conclusion, nivolumab persists in plasma after transplantation, binds to allogeneic T cells and generates an increased T-cell activation. This T-cell activation status can be mitigated with the use of PTCY, thus reducing the risk of aGVHD.
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