Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.
Adult
Aged
Apoptosis
B7-H1 Antigen
/ metabolism
DNA Copy Number Variations
Epstein-Barr Virus Infections
/ diagnosis
Female
Herpesvirus 4, Human
/ isolation & purification
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymphoproliferative Disorders
/ diagnosis
Male
Middle Aged
Prognosis
Programmed Cell Death 1 Receptor
/ metabolism
Epstein-Barr virus
FISH
PD-L1
PD1
diffuse large B-cell lymphoma
post-transplant lymphoproliferative disorders
prognosis
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
17
10
2018
revised:
04
02
2019
accepted:
07
03
2019
pubmed:
13
3
2019
medline:
28
4
2020
entrez:
13
3
2019
Statut:
ppublish
Résumé
The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
799-812Subventions
Organisme : Fondo de Investigación Sanitaria
ID : PI14/00333
Organisme : Red Temática de Investigación Cooperativa en Cáncer (RTICC)
ID : RD12/0036/0036
Organisme : European Regional Development Fund
Organisme : Colciencias (Colombian Department of Science, Technology and Innovation)
Organisme : Government of Colombia
ID : 728-2015
Organisme : Ministerio de Economía y Competitividad
ID : SAF2015-64885-R
Organisme : Instituto de Salud Carlos III
Informations de copyright
© 2019 John Wiley & Sons Ltd.
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