Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074–2.005; p = 0.048). In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

中文翻译：

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化疗治疗的睾丸癌幸存者的免疫发光特征和衰老生物标志物（p16INK4a）的表达。

细胞毒性化学疗法可以治愈晚期生殖细胞肿瘤。然而，癌症治疗可能会诱导细胞衰老并加速分子衰老。衰老过程意味着表达p16INK4a的细胞增多，淋巴细胞亚群发生变化。我们的目的是研究暴露于化学疗法的睾丸癌幸存者（TCS）潜在诱导过早免疫衰老。与年龄相匹配的健康对照相比，TCS化疗（≥3 BEP周期，无病≥3个月）的病例对照探索性研究。分离外周血单个核细胞，并通过流式细胞术分析淋巴细胞亚群。使用qPCR测量T细胞中的CDKN2A / p16INK4a表达。使用Wilcoxon符号秩和检验比较了TCS中淋巴细胞亚群的百分比和CDKN2A / p16INK4a表达。我们纳入了16个案例和16个控件。中位年龄为27岁（最少24岁，最长54岁），中位监测时间为26.5个月（最少3岁，最长192岁）。TCS的总T细胞和CD4 + T细胞在总淋巴细胞中的百分比较低。在CD4 + T淋巴细胞中，TCS的幼稚CD4 +较少，而记忆CD4 +细胞增加。在CD8 + T淋巴细胞中，TCS的幼稚细胞百分比降低，而CD8 + CD45RA + CD57 +细胞则增加。与对照相比，TCS还表现出记忆CD19 + B细胞减少。TCS中CDKN2A / p16INK4a在T细胞中的相对表达有所增加（平均值1.54；平均值的95％CI：1.074–2.005； p = 0.048）。在这项探索性研究中，TCS显示CDKN2A / p16INK4a表达增加，并且淋巴细胞表型与免疫衰老相关。有必要进行进一步的研究来定义这些改变在TCS中的临床意义。