The advancement of anti-cancer therapies has markedly improved the survival rate of children with cancer, making them long-term childhood cancer survivors (CCS). Nevertheless, these treatments cause a low-grade inflammatory state, determining inflamm-aging and, thus, favoring the early onset of chronic diseases normally associated with old age. Identification of novel and safer therapeutic strategies is needed to counteract and prevent inflamm-aging. Macrophages are cells involved in immune and inflammatory responses, with a pivotal role in iron metabolism, which is related to inflammation. We obtained macrophages from CCS patients and evaluated their phenotype markers, inflammatory states, and iron metabolism by Western blotting, ELISA, and iron assays. We observed a strong increase in classically activated phenotype markers (M1) and iron metabolism alteration in CCS, with an increase in intracellular iron concentration and inflammatory markers. These results suggest that the prevalence of M1 macrophages and alteration of iron metabolism could be involved in the worsening of inflammation in CCS. Therefore, we propose macrophages and iron metabolism as novel therapeutic targets to counteract inflamm-aging. To avoid toxic regimens, we tested some nutraceuticals (resveratrol, curcumin, and oil-enriched lycopene), which are already known to exert anti-inflammatory properties. After their administration, we observed a macrophage switch towards the anti-inflammatory phenotype M2, as well as reductions in pro-inflammatory cytokines and the intracellular iron concentration. Therefore, we suggest—for the first time—that nutraceuticals reduce inflammation in CCS macrophages through a novel anti-inflammatory mechanism of action, modulating iron metabolism.
抗癌疗法的进步显著提高了儿童癌症患者的生存率，使其成为长期存活的儿童癌症幸存者。然而，这些治疗手段会引发低度炎症状态，导致炎症性衰老，从而促使通常与老年相关的慢性疾病提前发生。因此，需要探索新型且更安全的治疗策略来对抗和预防炎症性衰老。巨噬细胞作为参与免疫和炎症反应的关键细胞，在铁代谢中发挥核心作用，而铁代谢与炎症过程密切相关。本研究从儿童癌症幸存者体内获取巨噬细胞，通过蛋白质印迹、酶联免疫吸附测定及铁含量检测等方法，评估其表型标志物、炎症状态及铁代谢水平。结果显示，幸存者体内经典激活表型标志物（M1型）显著增加，铁代谢发生紊乱，表现为细胞内铁浓度升高及炎症标志物增多。这些发现表明，M1型巨噬细胞的优势存在及铁代谢紊乱可能加剧儿童癌症幸存者的炎症状态。因此，我们提出将巨噬细胞和铁代谢作为对抗炎症性衰老的新型治疗靶点。为避免毒性治疗方案，我们测试了已知具有抗炎功能的营养保健品（白藜芦醇、姜黄素和富油番茄红素）。给药后观察到巨噬细胞向抗炎表型M2转化，同时促炎细胞因子和细胞内铁浓度均有所下降。本研究首次提出，营养保健品可通过调节铁代谢这一新型抗炎作用机制，减轻儿童癌症幸存者巨噬细胞的炎症反应。
肿瘤(癌症)患者之家