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Thyroid MALT lymphoma: self-harm to gain potential T-cell help.

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Wu, Fangtian 
Watanabe, Natsuko 
Tzioni, Maria-Myrsini 
Zhang, Chunye 


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.


Funder: CUH | Addenbrooke’s Charitable Trust, Cambridge University Hospitals (Addenbrooke’s Charitable Trust, Cambridge University Hospitals NHS Foundation Trust); doi:

Funder: Pathological Society of Great Britain and Ireland; doi:


B7-H1 Antigen, DNA-Binding Proteins, Dioxygenases, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, B-Cell, Marginal Zone, Molecular Targeted Therapy, Mutation, Receptors, Tumor Necrosis Factor, Member 14, T-Lymphocytes, Thyroid Neoplasms, Tumor Necrosis Factor alpha-Induced Protein 3

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Springer Science and Business Media LLC
Bloodwise (15019)
Blood Cancer UK (19010)
Bloodwise the Kay Kendall Leukaemia Fund the Addenbrooke’s Charitable Trust Pathological Society of Great Britain and Ireland