Childhood acute lymphoblastic leukemia (cALL) survivors suffer early-onset chronic diseases classically associated with aging. Normal aging is accompanied by organ dysfunctions, including immunological ones. We hypothesize that thymic immunosenescence occurs in cALL survivors and that its severity may correlate with early-onset chronic diseases. The PETALE study is a cALL survivor cohort with an extensive cardiovascular and metabolic evaluation. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants (n = 281) and cALL survivors (n = 248). We observed a systematic thymic immunoage accentuation in each cALL survivor compared to controls ranging from 5.9 to 88.3 years. The immunoage gain was independent of age at diagnosis and treatment modalities and was more severe for females. Thymic aging was associated with several pathophysiological parameters, was greater in survivors suffering from metabolic syndrome, but there was no significant association with global physical condition. The decrease in TREC was independent from blood cell counts, which were normal, suggesting a segmental aging of the thymic compartment. Indeed, increased plasmatic T cell regulatory cytokines IL-6, IL-7 and GM-CSF accompanied high immunoage gain. Our data reveal that cALL or its treatment trigger a rapid immunoage gain followed by further gradual thymic immunosenescence, similar to normal aging. This leads to an enduring shift in accentuated immunoage compared to chronological age. Thus, accentuated thymic immunosenescence is a hallmark of cALL survivorship and TREC levels could be useful immunosenescence biomarkers to help monitoring the health of cancer survivors.
儿童急性淋巴细胞白血病（cALL）幸存者常患有通常与衰老相关的早发性慢性疾病。正常衰老伴随着器官功能下降，包括免疫系统功能。我们假设cALL幸存者存在胸腺免疫衰老现象，且其严重程度可能与早发性慢性疾病相关。PETALE研究是一项针对cALL幸存者的队列研究，包含全面的心血管和代谢评估。通过检测胸腺免疫衰老生物标志物——信号结合T细胞受体删除环（TREC），发现在健康参与者（n=281）和cALL幸存者（n=248）中TREC与年龄高度相关。与对照组相比，每位cALL幸存者均表现出系统性胸腺免疫年龄加重现象（免疫年龄增加范围为5.9至88.3岁）。这种免疫年龄增长与确诊年龄及治疗方案无关，且女性患者更为显著。胸腺衰老与多种病理生理参数相关，在患有代谢综合征的幸存者中更为严重，但与整体身体状况无显著关联。TREC下降与血细胞计数无关（后者保持正常），提示胸腺区室存在选择性衰老。事实上，血浆调节性T细胞因子IL-6、IL-7和GM-CSF的升高伴随高免疫年龄增长。我们的数据表明，cALL或其治疗会引发快速免疫年龄增长，随后出现渐进性胸腺免疫衰老，这与正常衰老过程相似。相较于实际年龄，这导致免疫年龄持续偏移性加重。因此，加重的胸腺免疫衰老是cALL幸存者的标志性特征，TREC水平可作为有效的免疫衰老生物标志物，有助于监测癌症幸存者的健康状况。
肿瘤(癌症)患者之家