Unité Mixte de Recherche en Santé 938, Institut National de la Santé et de la Recherche Médicale, Site Saint-Antoine, Université Paris 6, Paris, France.
Liver Transpl. 2011 Mar;17(3):299-305. doi: 10.1002/lt.22232.
At present, no method is available for accurately monitoring the degree of immunosuppression induced by antirejection therapies. The aim of this study was to determine whether CD28 and CD38 expression by peripheral blood mononuclear cells could be useful in predicting the development of de novo malignancies after liver transplantation. Flow cytometry analysis was used to measure the expression of CD28 and CD38 by peripheral blood lymphocytes in 134 stable, long-term survivors of liver transplantation. Patients who developed a de novo malignancy after undergoing a medical checkup were entered into a cancer group. Twenty-two patients (16.4%) developed at least 1 de novo malignancy over a mean interval of 22 ± 14 months (1.2-49.4 months) after the checkup. The mean frequency of CD28(+)CD8(+) cells was significantly lower in the cancer group versus the noncancer group (39% ± 22 versus 51% ± 21, P = 0.008), but CD38 expression was similar in the 2 groups. Multivariate analysis indicated that an age greater than 50 years (odds ratio = 5.81) and a low frequency of CD28(+)CD8(+) cells at the time of the checkup (odds ratio =3.16) were the only significant predictors of the development of de novo malignancies (P = 0.027). The actuarial proportion of patients with de novo malignancies was significantly lower when the frequency of CD28(+)CD8(+) cells was greater than or equal to 40% instead of less than 40% (P = 0.01). Flow cytometry measurements of CD28 expression by peripheral blood lymphocytes may facilitate the identification of patients at a high risk of developing de novo malignancies. Further prospective studies are necessary to determine whether such measurements could have a place in routine clinical practice to enable the intensity of immunosuppression to be minimized in patients who have an increased risk of developing cancer.
目前，尚无方法可准确监测抗排斥治疗引起的免疫抑制程度。本研究旨在确定外周血单个核细胞 CD28 和 CD38 的表达是否可用于预测肝移植后新发恶性肿瘤的发生。采用流式细胞术分析了 134 例肝移植后长期稳定生存患者外周血淋巴细胞 CD28 和 CD38 的表达。在体检后发生新发恶性肿瘤的患者被纳入癌症组。22 例患者（16.4%）在体检后平均 22±14 个月（1.2-49.4 个月）内至少发生 1 例新发恶性肿瘤。癌症组 CD28(+)CD8(+)细胞的频率明显低于非癌症组（39%±22%比 51%±21%，P=0.008），但两组间 CD38 的表达相似。多变量分析表明，年龄大于 50 岁（比值比=5.81）和体检时 CD28(+)CD8(+)细胞频率低（比值比=3.16）是新发恶性肿瘤发生的唯一显著预测因素（P=0.027）。当 CD28(+)CD8(+)细胞频率大于或等于 40%而非小于 40%时，新发恶性肿瘤患者的累积比例明显降低（P=0.01）。外周血淋巴细胞 CD28 表达的流式细胞术测量可能有助于识别发生新发恶性肿瘤风险较高的患者。需要进一步的前瞻性研究来确定此类测量是否可在常规临床实践中发挥作用，以便在发生癌症风险增加的患者中最小化免疫抑制强度。
