Poster Presentation Melbourne Immunotherapy Network Winter Symposium 2021

Checkpoint inhibitor immunotherapy cause ovarian dysfunction in tumour bearing mice: consequences for fertility of female cancer survivors (#126)

Amy L Winship 1 , Lauren R Alesi 1 , Sneha Sant 2 , Jessica Stringer 1 , Teharn Hegarty 1 , Meaghan Griffiths 1 , Sherene Loi 2 , Karla Hutt 1
  1. Department of Anatomy & Developmental Biology, Monash University, Clayton, VIC , Australia
  2. Division of Clinical Medicine and Research, Peter MacCallum Cancer Centre, University of Melbourne, Parkville, VIC, Australia

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. Whilst immunotherapies are increasingly becoming a standard of care for many tumour types – including in the curative setting – their impacts on ovarian function and fertility are unknown. We therefore evaluated the effect of immune checkpoint inhibitors – anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies – on the ovary using tumour-bearing mouse models. Our analyses reveal that immune checkpoint inhibition increases immune cell infiltration and TNF-α expression within the ovary, diminishes the ovarian follicular reserve which supplies all mature ovulatory oocytes to sustain fertility, and impairs the ability of oocytes to mature and ovulate. These data demonstrate that immune checkpoint inhibitors have the potential to impair both the immediate and future fertility of young women. Hence, fertility preservation should be strongly considered for women receiving these immunotherapies, and investigation of preventative strategies prioritised in future studies.