Frascatani Rachele, Colella Marco, Monteleone Giovanni
Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Gastroenterology Unit, Fondazione Policlinico "Tor Vergata", 00133 Rome, Italy.
Cancers (Basel). 2024 Dec 5;16(23):4068. doi: 10.3390/cancers16234068.
Colorectal cancer (CRC) is one of the most frequent neoplasms and a major cause of cancer death worldwide. Despite recent advances in treatment approaches, the prognosis of advanced CRC remains poor, thus indicating the necessity of more effective treatments for CRC patients. CRC cells produce high levels of hepcidin, a peptide hormone that binds to the membrane-bound ferroportin and promotes its internalization and degradation, thus sequestering iron into the cancer cells with the downstream effect of enhancing tumor growth. Additionally, CRC cell-expressed hepcidin prolongs cell survival and, by targeting both CD8+ T cells and myeloid cells, restrains the induction of an efficient immune response against tumor antigens. The greatest expression of hepcidin is found in patients with metastatic CRC, and CRC patients with high hepcidin content have a worse survival rate than those with low hepcidin content. In the present article, we review the data supporting the prominent role of hepcidin in colon tumorigenesis and discuss how hepcidin inhibitors can help treat CRC patients in the metastatic setting with particular regard to the impact of hepcidin modulation on immunotherapeutic outcomes.
结直肠癌（CRC）是全球最常见的肿瘤之一，也是癌症死亡的主要原因。尽管近年来治疗方法取得了进展，但晚期CRC的预后仍然很差，这表明有必要为CRC患者提供更有效的治疗方法。CRC细胞产生高水平的铁调素，这是一种肽激素，它与膜结合的铁转运蛋白结合，促进其内化和降解，从而将铁隔离到癌细胞中，具有增强肿瘤生长的下游效应。此外，CRC细胞表达的铁调素可延长细胞存活时间，并通过靶向CD8+T细胞和髓样细胞，抑制针对肿瘤抗原的有效免疫反应的诱导。铁调素的最大表达见于转移性CRC患者，铁调素含量高的CRC患者的生存率低于铁调素含量低的患者。在本文中，我们回顾了支持铁调素在结肠肿瘤发生中突出作用的数据，并讨论了铁调素抑制剂如何有助于治疗转移性CRC患者，特别关注铁调素调节对免疫治疗结果的影响。
