机构：[1]Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK[2]Department of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, PR China江苏省人民医院[3]Department of Internal Medicine, Ito Hospital, Tokyo, Japan[4]Department of Pathology, University College London, London, UK[5]Department of Haematology, Hebei General Hospital, Shijiazhuang, Hebei, PR China[6]Indica Labs, Albuquerque, NM, USA[7]Department of Surgery, Ito Hospital, Tokyo, Japan[8]Department of Pathology, West China Hospital, Sichuan University, Chengdu, PR China四川大学华西医院[9]Molecular Malignancy Laboratory, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK[10]Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK[11]Institute of Pathology and Microbiology, Wilhelminenspital, Vienna, Austria[12]Department of Pathology, Eye and ENT Hospital, Fudan University, Shanghai, PR China[13]Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan[14]Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria[15]Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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.
基金：
The research in MQD’s lab was supported by grants from
Blood Cancer UK (13006, 19010), the Kay Kendall Leukaemia Fund
(KKLF1141) UK. FW was supported by a research fellowship from
the China Scholarship Council, and a research award from the
Addenbrooke’s Charitable Trust. WY was supported by a research
fellowship from the China Scholarship Council, and an International
Collaborative Award from the Pathological Society of Great Britain
and Ireland, UK. The Human Research Tissue Bank is supported by
the NIHR Cambridge Biomedical Research Centre.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|1 区医学
小类|1 区肿瘤学1 区血液学
最新[2023]版：
大类|1 区医学
小类|1 区血液学1 区肿瘤学
第一作者：
第一作者机构：[1]Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK[2]Department of Hematology, Pukou CLL Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, PR China
通讯作者：
通讯机构：[1]Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK[15]Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
推荐引用方式(GB/T 7714)：
Wu Fangtian,Watanabe Natsuko,Tzioni Maria-Myrsini,et al.Thyroid MALT lymphoma: self-harm to gain potential T-cell help.[J].Leukemia.2021,35(12):3497-3508.doi:10.1038/s41375-021-01289-z.
APA：
Wu Fangtian,Watanabe Natsuko,Tzioni Maria-Myrsini,Akarca Ayse,Zhang Chunye...&Du Ming-Qing.(2021).Thyroid MALT lymphoma: self-harm to gain potential T-cell help..Leukemia,35,(12)
MLA：
Wu Fangtian,et al."Thyroid MALT lymphoma: self-harm to gain potential T-cell help.".Leukemia 35..12(2021):3497-3508
医学