Berglund David, Kinch Amelie, Edman Elin, Backlin Carin, Enblad Gunilla, Larsson Erik, Molin Daniel, Pauksens Karlis, Sundström Christer, Baecklund Eva
1 Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden. 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 3 Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 4 Halmstad Hospital, Halmstad, Sweden. 5 Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 6 Section of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
Transplantation. 2015 May;99(5):1036-42. doi: 10.1097/TP.0000000000000415.
The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.
Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.
Based on a cutoff level of 29 FoxP3 cells per mm, most (80%) of the PTLDs were FoxP3. Forty-seven of 74 PTLDs displayed no FoxP3 cells at all. The frequency of FoxP3 cells did not influence median overall survival. The FoxP3 PTLDs were more frequently of T-cell phenotype (P = 0.04), located at the graft (P = 0.03), occurred earlier after transplantation (P = 0.04), were more likely to develop in lung recipients (P = 0.04), and in patients that had received anti-T-cell globulin as induction therapy (P = 0.02). The FoxP3 PTLDs were associated with hepatitis C seropositivity (P = 0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.
Our findings suggest that intratumoral FoxP3 Tregs do not influence survival in patients with PTLD. FoxP3 Tregs are rare in PTLD, possibly because of heavy immunosuppression.
调节性T细胞（Tregs）浸润于淋巴瘤中与某些类型淋巴瘤的较好预后相关，但它们在移植后淋巴组织增生性疾病（PTLDs）中的作用的相关知识有限。因此，我们研究了PTLD活检组织中Treg标志物叉头框蛋白3（FoxP3）的表达与生存率、PTLD亚型及临床特征之间的关联。
从瑞典一项基于人群的PTLD研究中纳入74例实体器官移植后有足够材料进行进一步分析的PTLD病例。对PTLD活检组织进行重新评估，并用236A/E7抗体染色以检测淋巴瘤组织中的FoxP3。从医疗记录中回顾性收集详细的临床数据。
基于每毫米29个FoxP3细胞的临界水平，大多数（80%）PTLD为FoxP3阳性。74例PTLD中有47例根本没有FoxP3细胞。FoxP3细胞的频率不影响中位总生存期。FoxP3阳性的PTLD更常为T细胞表型（P = 0.04），位于移植物处（P = 0.03），在移植后出现得更早（P = 0.04），更有可能在肺移植受者中发生（P = 0.04），以及在接受抗T细胞球蛋白作为诱导治疗的患者中发生（P = 0.02）。FoxP3阳性的PTLD与丙型肝炎血清学阳性相关（P = 0.03）。在多变量分析中，B细胞PTLD和丙型肝炎感染是FoxP3阳性的独立预测因素。
我们的研究结果表明，肿瘤内FoxP3 Tregs不影响PTLD患者的生存。FoxP3 Tregs在PTLD中很少见，可能是由于强效免疫抑制。
