文章目录

检查点抑制剂免疫疗法降低小鼠卵母细胞数量和质量

原文发布日期：2022-08-25

英文摘要：

摘要翻译：

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文章：

检查点抑制剂免疫疗法降低小鼠卵母细胞数量和质量

Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice

原文发布日期：2022-08-25

英文摘要：

Loss of fertility is a major concern for female reproductive-age cancer survivors, since a common side-effect of conventional cytotoxic cancer therapies is permanent damage to the ovary. While immunotherapies are increasingly becoming a standard of care for many cancers—including in the curative setting—their impacts on ovarian function and fertility are unknown. We evaluated the effect of immune checkpoint inhibitors blocking programmed cell death protein ligand 1 and cytotoxic T lymphocyte-associated antigen 4 on the ovary using tumor-bearing and tumor-free mouse models. We find that immune checkpoint inhibition increases immune cell infiltration and tumor necrosis factor-α expression within the ovary, diminishes the ovarian follicular reserve and impairs the ability of oocytes to mature and ovulate. These data demonstrate that immune checkpoint inhibitors have the potential to impair both immediate and future fertility, and studies in women should be prioritized. Additionally, fertility preservation should be strongly considered for women receiving these immunotherapies, and preventative strategies should be investigated in future studies.

摘要翻译：

放疗后女性生殖年龄段癌症患者的生育能力丧失是一个主要担忧，因为常规化疗药物作为常规治疗手段之一会永久损害卵巢功能。尽管免疫治疗已经成为多种癌症治疗方案中的标准做法——包括治愈性治疗方案，但目前尚不清楚这些免疫治疗对卵巢功能和生育能力会产生什么影响。本研究通过肿瘤携带型和肿瘤切除小鼠模型评估了抑制程序细胞死亡蛋白-1（PD-L1）结合位点的免疫检查点抑制剂和CD8 T淋巴细胞相关抗原4（CTLA4）阻断剂对卵巢的影响，发现免疫检查点抑制可增加卵巢内免疫细胞浸润及肿瘤坏死因子α表达，减少卵巢储备池数量，并削弱卵母细胞成熟和排卵的能力。这些研究结果表明，免疫检查点抑制剂可能会影响患者即刻及未来生育能力，并应在女性中进行重点研究。此外，在接受此类免疫治疗的女性中应优先考虑生育能力保护措施，并在未来的研究中探索预防性策略。