Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders: Clinical Features and Survival Outcomes
Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders: Clinical Features and Survival Outcomes
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移植后淋巴增殖性疾病中肿瘤内叉头盒蛋白 3 的表达：临床特征和生存结果
作者：
D. Berglund;A. Kinch;Elin Edman;C. Backlin;G. Enblad;E. Larsson;D. Molin;K. Pauksens;C. Sundström;E. Baecklund
调节性T细胞（Tregs）在淋巴瘤中的浸润与某些类型淋巴瘤的预后良好相关，但对其在移植后淋巴增生性疾病（PTLDs）中的作用的了解有限。因此，我们研究了PTLD活检中Treg标记叉头盒蛋白3 （FoxP3）的表达与生存、PTLD亚型和临床特征之间的关系。方法从瑞典一项以人群为基础的移植后PTLD的研究中纳入74例有足够资料进行进一步分析的实体器官移植后PTLD病例。重新评估PTLD活检，并用236A/E7抗体染色检测淋巴瘤组织中的FoxP3。回顾性收集详细的临床资料。结果基于每mm2 29个FoxP3+细胞的临界值，大多数（80%）ptld为FoxP3−。74个PTLDs中有47个未见FoxP3+细胞。FoxP3+细胞的频率不影响中位总生存期。FoxP3−PTLDs的t细胞表型更常见（P = 0.04），位于移植物（P = 0.03），移植后发生时间更早（P = 0.04），更容易在肺受体（P = 0.04）和接受抗t细胞球蛋白诱导治疗的患者中发生（P = 0.02）。FoxP3+ PTLDs与丙型肝炎血清阳性相关（P = 0.03）。在多变量分析中，b细胞PTLD和丙型肝炎感染是FoxP3阳性的独立预测因子。结论肿瘤内FoxP3+ Tregs不影响PTLD患者的生存。FoxP3+ Tregs在PTLD中很少见，可能是由于严重的免疫抑制。
Background 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. Methods 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. Results Based on a cutoff level of 29 FoxP3+ cells per mm2, 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. Conclusion 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.
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影响因子：
120.7
作者：
Engels, Eric A.;Pfeiffer, Ruth M.;Fraumeni, Joseph F., Jr.;Kasiske, Bertram L.;Israni, Ajay K.;Snyder, Jon J.;Wolfe, Robert A.;Goodrich, Nathan P.;Bayakly, A. Rana;Clarke, Christina A.;Copeland, Glenn;Finch, Jack L.;Fleissner, Mary Lou;Goodman, Marc T.;Kahn, Amy;Koch, Lori;Lynch, Charles F.;Madeleine, Margaret M.;Pawlish, Karen;Rao, Chandrika;Williams, Melanie A.;Castenson, David;Curry, Michael;Parsons, Ruth;Fant, Gregory;Lin, Monica
通讯作者：
Lin, Monica
影响因子：
45.3
作者：
Greaves, Paul;Clear, Andrew;Gribben, John G.
通讯作者：
Gribben, John G.
影响因子：
20.3
作者：
Hans, CP;Weisenburger, DD;Chan, WC
通讯作者：
Chan, WC
影响因子：
32.4
作者：
Riley, James L.;June, Carl H.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.
影响因子：
20.3
作者：
Feng, Xingmin;Kajigaya, Sachiko;Young, Neal S.
通讯作者：
Young, Neal S.