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障碍，包括免疫功能障碍。我们假设胸腺免疫衰老发生在 cALL 幸存者中，其严重程度可能与早发性慢性疾病相关。PETALE 研究是一个 cALL 幸存者队列，具有广泛的心血管和代谢评估。评估了胸腺免疫衰老生物标志物信号关节 T 细胞受体切除圈 （TREC），该标志与健康参与者 （n = 281） 和 cALL 幸存者 （n = 248） 的年龄高度相关。我们观察到每个 cALL 幸存者与 5.9 至 88.3 岁的对照组相比，系统性胸腺免疫年龄增强。免疫年龄增加与诊断和治疗方式的年龄无关，女性更严重。胸腺衰老与几个病理生理参数相关，在患有代谢综合征的幸存者中更大，但与整体身体状况没有显着关联。TREC 的降低与血细胞计数无关，血细胞计数是正常的，表明胸腺隔室的节段性老化。事实上，血浆 T 细胞调节细胞因子 IL-6 、 IL-7 和 GM-CSF 的增加伴随着免疫力的高增益。我们的数据显示，cALL 或其治疗会触发免疫年龄的快速增加，然后是进一步逐渐的胸腺免疫衰老，类似于正常衰老。与实际年龄相比，这导致增强免疫年龄的持久变化。因此，增强的胸腺免疫衰老是 cALL 幸存者的标志，TREC 水平可能是有用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。