TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.
Blood
; 128(1): 72-81, 2016 07 07.
Article
en En
| MEDLINE
| ID: mdl-27103745
ABSTRACT
Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfoma Folicular
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Trasplante de Células Madre Hematopoyéticas
/
Miembro 14 de Receptores del Factor de Necrosis Tumoral
/
Enfermedad Injerto contra Huésped
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Blood
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido