Caserta Santino, Cancemi Gabriella, Murdaca Giuseppe, Stagno Fabio, Di Gioacchino Mario, Gangemi Sebastiano, Allegra Alessandro
Hematology Unit, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, via Consolare Valeria, 98125 Messina, Italy.
Department of Internal Medicine, University of Genova, 16126 Genova, Italy.
Biomedicines. 2024 Sep 15;12(9):2106. doi: 10.3390/biomedicines12092106.
In recent years, cancer management has benefitted from new effective treatments, including immunotherapy. While these therapies improve cancer survival rates, they can alter immune responses and cause long-term side effects, of which gonadotoxic effects and the potential impact on male and female fertility are growing concerns. Immunotherapies, such as immune checkpoint inhibitors, immunomodulators, monoclonal antibodies, and CAR-T, can lead to elevated levels of proinflammatory cytokines and immune-related adverse events that may exacerbate fertility problems. Immunotherapy-related inflammation, characterized by cytokine imbalances and the activation of pathways such as AMPK/mTOR, has been implicated in the mechanisms of fertility impairment. In men, hypospermatogenesis and aspermatogenesis have been observed after treatment with immune checkpoint inhibitors, by direct effects on the gonads, particularly through the inhibition of cytotoxic T lymphocyte antigen-4. In women, both damage to ovarian reserves, recurrent pregnancy loss, and implantation failure have been documented, secondary to a complex interplay between immune cells, such as T cells and uterine NK cells. In this review, the impact of immunotherapy on fertility in patients with hematological cancers was analyzed. While this area is still underexplored, fertility preservation methods remain crucial. Future studies should investigate immunotherapy's effects on fertility and establish standardized preservation protocols.
近年来，癌症治疗受益于包括免疫疗法在内的新型有效治疗方法。虽然这些疗法提高了癌症生存率，但它们会改变免疫反应并导致长期副作用，其中性腺毒性作用以及对男性和女性生育能力的潜在影响日益受到关注。免疫疗法，如免疫检查点抑制剂、免疫调节剂、单克隆抗体和嵌合抗原受体T细胞（CAR-T），可导致促炎细胞因子水平升高和免疫相关不良事件，这可能会加剧生育问题。以细胞因子失衡和AMPK/mTOR等信号通路激活为特征的免疫治疗相关炎症，已被认为与生育功能受损机制有关。在男性中，使用免疫检查点抑制剂治疗后，观察到精子发生减少和无精子发生，这是由于对性腺的直接影响，特别是通过抑制细胞毒性T淋巴细胞抗原-4。在女性中，卵巢储备受损、复发性流产和着床失败均有记录，这是T细胞和子宫自然杀伤细胞等免疫细胞之间复杂相互作用的结果。在这篇综述中，分析了免疫疗法对血液系统癌症患者生育能力的影响。虽然这一领域仍未得到充分探索，但生育力保存方法仍然至关重要。未来的研究应调查免疫疗法对生育能力的影响，并建立标准化的保存方案。
