Parity and lactation induce T cell mediated breast cancer protection
- Author(s)
- Virassamy, B; Caramia, F; Savas, P; Harris, MA; Pan, JW; Wang, J; Brown, E; O'Malley, MMR; van Geelen, CT; Hun, M; Burn, TN; Sant, S; Ballan, JD; Kay, J; Lara Gonzalez, LE; Clarke, K; Aw Yeang, HX; Idrizi, R; Jana, M; Challice, DJ; Salgado, R; Thorne, H; kConFab Consortium; Poliness, C; Nightingale, S; Teo, SH; Speed, TP; Visvader, J; Neeson, PJ; Darcy, PK; Mackay, LK; Loi, S;
- Journal Title
- Nature
- Publication Type
- Online publication before print
- Abstract
- Parity and breastfeeding reduce the risk of breast cancer, particularly triple-negative breast cancer (TNBC)(1,2), yet the immunological mechanisms underlying this protection remain unclear. Here, we show that parity induces an accumulation of CD8(+) T cells, including cells with a tissue-resident memory (T(RM))-like phenotype within human normal breast tissue. In murine models, pregnancy followed by lactation and involution drove the accumulation of CD8⁺ T cells in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune cell infiltration, effects that were abrogated by CD8⁺ T cell depletion. Importantly, this CD8(+) T cell dependent tumour control was only observed following a complete cycle of lactation and involution. Consistent with this, primary TNBCs from parous women exhibited greater T cell infiltration and improved clinical outcomes. Together these findings, spanning preclinical models and over 1000 patient samples, provide new insight into how reproductive history shapes breast immunity, positioning CD8⁺ T cells as key mediators of parity-associated protection and informing novel strategies for both prevention and treatment of breast cancer.
- Department(s)
- Laboratory Research; Surgical Oncology
- Publisher's Version
- https://doi.org/10.1038/s41586-025-09713-5
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-11-25 12:06:37
Last Modified: 2025-11-25 12:06:47