Journal article
Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice.
Amy L Winship, Lauren R Alesi, Sneha Sant, Jessica M Stringer, Aldana Cantavenera, Teharn Hegarty, Carolina Lliberos Requesens, Seng H Liew, Urooza Sarma, Meaghan J 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
Nature Cancer | Nature Research | Published : 2022
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-α expression with..
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Grants
Awarded by National Breast Cancer Foundation
Funding Acknowledgements
The authors acknowledge the technical support of the Monash Animal Research Platform, Monash Histology Platform, Monash FlowCore Platform, Monash Micro Imaging Facility, Peter MacCallum Cancer Centre Animal Research Platform and Peter MacCallum Cancer Centres Flow Facility. We thank P. Bouillet and WEHI Bioservices for the provision of large numbers of BID-deficient mice. We also thank H. Thorne, E. Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, the National Breast Cancer Foundation of Australia (NBCF), Cancer Australia and the National Institutes of Health (USA) for their contributions to this resource, and the many families who contribute to kConFab. Fig. 6h and the Supplementary Fig. 1 were created using BioRender.com. This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government National Health and Medical Research Council (NHMRC) IRIISS. This work was supported by NBCF funding grant no. IIRS-22-092. A.L.W. is supported by DECRA funding grant no. DE21010037 from the Australian Research Council (ARC). L.R.A. is supported by an Australian Government Research Training Program Scholarship and a Monash Graduate Excellence Scholarship. K.-A.P. is an NHMRC Leadership Fellow. S.L. is supported by the NBCF. A.S. is supported by an NHMRC Program Grant no. 1113133, NHMRC Fellowship no. 1116937 and NHMRC Investigator Grant no. 2007887. K.J.H. is supported by an ARC Future Fellowship grant no. FT190100265.