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肿瘤免疫治疗对生育力的影响:聚焦血液系统恶性肿瘤

英文原题:The Effects of Cancer Immunotherapy on Fertility: Focus on Hematological Malignancies.

查看英文原题

The Effects of Cancer Immunotherapy on Fertility: Focus on Hematological Malignancies.

PubMed 2024/09/15(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

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中文摘要

近年来,肿瘤治疗受益于新的有效疗法,包括免疫治疗。尽管这些疗法提高了癌症生存率,但它们可能改变免疫反应并导致长期副作用,其中性腺毒性作用及其对男性和女性生育能力的潜在影响日益受到关注。免疫治疗,如免疫检查点抑制剂、免疫调节剂、单克隆抗体和 CAR-T,可导致促炎细胞因子水平升高和免疫相关不良事件,从而可能加剧生育问题。免疫治疗相关炎症以细胞因子失衡和 AMPK/mTOR 等通路激活为特征,已被认为与生育力受损的机制有关。在男性中,接受免疫检查点抑制剂治疗后已观察到精子生成减少和无精子生成,这是通过对性腺的直接作用,特别是通过抑制 cytotoxic T lymphocyte antigen-4 实现的。在女性中,已有卵巢储备受损、复发性流产和着床失败的报道,继发于 T 细胞和子宫 NK 细胞等免疫细胞之间复杂的相互作用。本综述分析了免疫治疗对血液系统恶性肿瘤患者生育力的影响。尽管该领域仍探索不足,但生育力保存方法仍然至关重要。未来研究应探讨免疫治疗对生育力的影响,并建立标准化的保存方案。

展开英文摘要原文

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.

论文信息

作者
Caserta S、Cancemi G、Murdaca G、Stagno F、Di Gioacchino M、Gangemi S、Allegra A
单位
Hematology Unit, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, via Consolare Valeria, 98125 Messina, Italy.Italy
文献类型
综述
期刊
Biomedicines2024 Sep 15
原文标识
PubMed 39335619 · DOI 10.3390/biomedicines12092106