Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice

Winship, AL; Alesi, LR; Sant, S; Stringer, JM; Cantavenera, A; Hegarty, T; Lliberos Requesens, C; Liew, SH; Sarma, U; Griffiths, MJ; Zerafa, N; Fox, SB; Brown, E; Caramia, F; Zareie, P; La Gruta, NL; Phillips, KA; Strasser, A; Loi, S; Hutt, KJ

Author(s): Winship, AL; Alesi, LR; Sant, S; Stringer, JM; Cantavenera, A; Hegarty, T; Lliberos Requesens, C; Liew, SH; Sarma, U; Griffiths, MJ; Zerafa, N; Fox, SB; Brown, E; Caramia, F; Zareie, P; La Gruta, NL; Phillips, KA; Strasser, A; Loi, S; Hutt, KJ;
Details: Publication Year 2022-08,Volume 3,Issue #8,Page 932-944
Journal Title: Nature Cancer
Publication Type: Research article
Abstract: 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-alpha 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.
Keywords: Animals; Female; *Fertility Preservation; Humans; Immune Checkpoint Inhibitors; Immunotherapy/adverse effects; Mice; *Neoplasms; Oocytes/pathology
Department(s): Laboratory Research; Pathology; Medical Oncology
PubMed ID: 36008687
Publisher's Version: https://doi.org/10.1038/s43018-022-00413-x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-09 07:31:47

Last Modified: 2025-05-09 07:33:16