Thyroid MALT lymphoma: self-harm to gain potential T-cell help.
B7-H1 Antigen
/ genetics
DNA-Binding Proteins
/ genetics
Dioxygenases
/ genetics
High-Throughput Nucleotide Sequencing
/ methods
Humans
Lymphoma, B-Cell, Marginal Zone
/ genetics
Molecular Targeted Therapy
Mutation
Receptors, Tumor Necrosis Factor, Member 14
/ genetics
T-Lymphocytes
/ immunology
Thyroid Neoplasms
/ genetics
Tumor Necrosis Factor alpha-Induced Protein 3
/ genetics
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
31
01
2021
accepted:
06
05
2021
revised:
29
04
2021
pubmed:
23
5
2021
medline:
29
1
2022
entrez:
22
5
2021
Statut:
ppublish
Résumé
The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%), and TNFAIP3 (30%) in thyroid MALT lymphoma. CD274 was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274 mutation/deletion and TNFRSF14 mutation (p = 0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274/TNFRSF14 genetic abnormalities than those without these changes. Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto's thyroiditis (p = 0.01, p = 0.04, respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate (p = 0.0001). In conclusion, CD274/TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.
Identifiants
pubmed: 34021249
doi: 10.1038/s41375-021-01289-z
pii: 10.1038/s41375-021-01289-z
pmc: PMC8632687
mid: EMS123947
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
DNA-Binding Proteins
0
Receptors, Tumor Necrosis Factor, Member 14
0
TNFRSF14 protein, human
0
Dioxygenases
EC 1.13.11.-
TET2 protein, human
EC 1.13.11.-
TNFAIP3 protein, human
EC 3.4.19.12
Tumor Necrosis Factor alpha-Induced Protein 3
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3497-3508Subventions
Organisme : Blood Cancer UK
ID : 13006
Pays : United Kingdom
Organisme : Blood Cancer UK
ID : 15019
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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