Transplantation Research Immunology Group, Nuffield Department of Surgery, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom.
J Am Soc Nephrol. 2010 Apr;21(4):713-22. doi: 10.1681/ASN.2009060669. Epub 2010 Jan 28.
Cutaneous squamous cell cancer (SCC) affects up to 30% of kidney transplant recipients (KTRs) within 10 years of transplantation. There are no reliable clinical tests that predict those who will develop multiple skin cancers. High numbers of regulatory T cells associate with poor prognosis for patients with cancer in the general population, suggesting their potential as a predictive marker of cutaneous SCC in KTRs. We matched KTRs with (n = 65) and without (n = 51) cutaneous SCC for gender, age, and duration of immunosuppression and assessed several risk factors for incident SCC during a median follow-up of 340 days. Greater than 35 peripheral FOXP3(+)CD4(+)CD127(low) regulatory T cells/microl, <100 natural killer cells/microl, and previous SCC each significantly associated with increased risk for new cutaneous SCC development (hazard ratio [HR] 2.48 [95% confidence interval (CI) 1.04 to 5.98], HR 5.6 [95% CI 1.31 to 24], and HR 1.33 [95% CI 1.15 to 1.53], respectively). In addition, the ratio of CD8/FOXP3 expression was significantly lower in cutaneous SCC excised from KTRs (n = 25) compared with matched SCC from non-KTRs (n = 25) and associated with development of new cutaneous SCCs. In summary, monitoring components of the immune system can predict development of cutaneous SCC among KTRs.
皮肤鳞状细胞癌 (SCC) 在移植后 10 年内影响多达 30%的肾移植受者 (KTR)。目前尚无可靠的临床检测方法可以预测哪些患者会患上多发性皮肤癌。大量调节性 T 细胞与一般人群中癌症患者的预后不良相关,这表明它们可能成为 KTR 皮肤 SCC 的预测标志物。我们匹配了 KTR 患者(n=65)和无皮肤 SCC 的患者(n=51)的性别、年龄和免疫抑制持续时间,并在中位数为 340 天的随访期间评估了几种 SCC 发病的危险因素。外周血 FOXP3(+)CD4(+)CD127(low)调节性 T 细胞/µl 大于 35、自然杀伤细胞/µl 小于 100 和先前患有 SCC 均与新的皮肤 SCC 发展风险增加显著相关(风险比 [HR] 2.48 [95%置信区间 (CI) 1.04 至 5.98]、HR 5.6 [95%CI 1.31 至 24]和 HR 1.33 [95%CI 1.15 至 1.53])。此外,与非 KTR 相匹配的 SCC 相比,从 KTR 切除的皮肤 SCC(n=25)中 CD8/FOXP3 表达的比值显著降低,并且与新的皮肤 SCC 的发展相关。总之,监测免疫系统的成分可以预测 KTR 中皮肤 SCC 的发生。