Parity and lactation induce T-cell-mediated breast cancer protection

Virassamy, B; kConFab, Consortium; Caramia, F; Savas, P; Harris, MA; Pan, JW; Wang, J; Brown, E; O&#39;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; Poliness, C; Nightingale, S; Teo, SH; Speed, TP; Visvader, J; Neeson, PJ; Darcy, PK; Mackay, LK; Loi, S

Author(s): Virassamy, B; kConFab, Consortium; 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; Poliness, C; Nightingale, S; Teo, SH; Speed, TP; Visvader, J; Neeson, PJ; Darcy, PK; Mackay, LK; Loi, S;
Details: Publication Year 2026-01,Volume 649,Issue #8096,Page 449-459
Journal Title: Nature
Publication Type: Oct 20
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 is associated with increased numbers of CD8(+) T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue. In mouse 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 observed only after a complete cycle of lactation and involution. Consistent with this, primary triple-negative breast cancers from parous women exhibited greater T cell infiltration and improved clinical outcomes. Together, these findings, spanning preclinical models and over 1,000 patient samples, provide insights into how reproductive history shapes breast immunity, positioning CD8(+) T cells as key mediators of parity-associated protection and informing strategies for both the prevention and the treatment of breast cancer.
Publisher: Springer Nature
Keywords: Female; Animals; *CD8-Positive T-Lymphocytes/immunology/cytology; *Parity/immunology; Humans; Mice; *Lactation/immunology/physiology; *Triple Negative Breast Neoplasms/immunology/pathology/prevention & control; Pregnancy; *Breast Neoplasms/immunology/prevention & control/pathology; Adult; Immunologic Memory; Disease Models, Animal
Research Division(s): Cancer Biology and Stem Cells; Bioinformatics and Computational Biology
PubMed ID: 41115453
Publisher's Version: https://doi.org/10.1038/s41586-025-09713-5
Open Access at Publisher's Site: https://doi.org/10.1038/s41586-025-09713-5.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-11-03 09:22:08

Last Modified: 2026-01-29 01:41:42