免疫系统
细胞毒性T细胞
保持生育能力
免疫疗法
卵泡期
免疫检查点
生物
癌症研究
卵巢
免疫学
癌症
肿瘤科
生育率
医学
内科学
内分泌学
人口
体外
生物化学
环境卫生
作者
Amy Winship,Lauren R. Alesi,Sneha Sant,Jessica M Stringer,Aldana Cantavenera,Teharn Hegarty,C Requeséns,Seng H. Liew,Urooza C. Sarma,Meaghan Griffiths,Nadeen Zerafa,Stephen B. Fox,Emmaline Brown,Franco Caramia,Pirooz Zareie,Nicole L. La Gruta,Kelly‐Anne Phillips,Andreas Strasser,Sherene Loi,Karla J. Hutt
出处
期刊:Nature cancer
[Springer Nature]
日期:2022-08-25
卷期号:3 (8): 1-13
被引量:25
标识
DOI:10.1038/s43018-022-00413-x
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.
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