Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients
Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients
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DOI：
10.1111/j.1432-2277.2012.01521.x
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发表时间：
2012-09-01
影响因子：
3.1
通讯作者：
Ducloux, Didier
中科院分区：
文献类型：
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作者：
Courivaud, Cecile;Bamoulid, Jamal;Ducloux, Didier
巨细胞病毒（CMV）在肿瘤发生中的作用存在争议。我们研究了巨细胞病毒是否可能导致肾移植受者的癌症发生。我们对1995年1月至2006年12月期间接受肾移植的455例连续患者进行了前瞻性队列研究。评估了所有癌症和癌症类型。淋巴细胞表型和细胞因子的生产进行了分析，根据CMV状态在该队列的一个子集的人口。平均随访时间为84 +/- 29个月。119例癌症（26.2%）发生在研究随访期间。CMV暴露患者的癌症累积发病率较高（30.4% vs. 20%; P = 0.018）。CMV暴露患者发生癌症的平均时间短于CMV初治患者（4.7 +/- 2.6 vs. 6.7 +/- 2.8; P = 0.001）。考克斯回归分析显示，移植前CMV暴露（HR，1.83; 95% CI，1.17 - 2.88; P = 0.009）和移植后CMV复制（HR，2.17; 95% CI，1.02 - 4.59; P = 0.044）均为癌症的危险因素。在CD 8 + T细胞中，评估为CD 57 + CD 28-的耗尽的T细胞在CMV暴露患者中扩增（26 +/-20vs.9 +/- 8%; P < 0.0001），而CD 8 + CD 57 + IL 2-细胞在CMV暴露患者中更常见。我们的研究结果高度提示CMV增加了移植后患癌症的风险。
The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 +/- 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P = 0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naive patients (4.7 +/- 2.6 vs. 6.7 +/- 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.172.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.024.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 +/- 20 vs. 9 +/- 8%; P < 0.0001), whereas CD8+CD57+IL2- cells were more frequent in CMV-exposed patients. Our results highly suggest that CMV increases the risk of cancer after transplantation.