CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk Patients
CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk Patients
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DOI：
10.1681/asn.2015030250
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发表时间：
2016-05-01
影响因子：
13.6
通讯作者：
Wood, Kathryn J.
中科院分区：
文献类型：
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作者：
Bottomley, Matthew J.;Harden, Paul N.;Wood, Kathryn J.
在长期肾移植受者中，与恶性肿瘤相关的大多数发病率是由于皮肤鳞状细胞癌（SCC）。然而，以前确定的SCC风险分层措施使用有限。我们假设衰老的终末分化的CD 8（+）T细胞比例增加将识别出肾移植受者SCC风险升高。从117例稳定的SCC高危移植受者中分离外周血淋巴细胞，并通过流式细胞术进行表型分析。对参与者进行前瞻性随访，以了解SCC的发展。采用考克斯回归分析评估变量的预测值。移植和登记时的年龄、透析持续时间和既往疾病可预测随访期间SCC的发展。以前发表的基于临床表型的风险评分失去了预测价值，删除了年龄作为协变量。表达CD 57的CD 8（+）T细胞的百分比是未来SCC的最强免疫学预测因子，并与CD 8（+）T细胞分化的增加相关。我们将受试者分为大多数（CD 57 hi）和少数（CD 571 o）表达CD 57的CD 8（+）T细胞的受试者; CD 57 hi受试者在随访期间更有可能发展为SCC（风险比，2.9; 95%置信区间，1.0至8.0），独立于潜在的混杂因素，并且倾向于发展为早期复发。CD 57 hi表型随时间推移而稳定，并与年龄增加和巨细胞病毒血清阳性相关。我们的研究结果表明，CD 57 hi表型是长期高危肾移植受者中SCC发展和复发的强有力预测因子。这些信息可以帮助识别接受者谁可能受益于密集的皮肤病筛查和免疫抑制减少。
Most morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8(+) T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57-expressing CD8(+) T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8(+) T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD571o) of CD8(+) T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction.