Pregnancy-induced tissue-resident memory-like T cells contribute to tumor control in breast cancer

Hussain, T; Pereira, M; Chisanga, D; Dawson, CA; Tang, A; Thilakasiri, P; Singh, J; Ruppert, M; Davey, A; Man, K; Murer, P; Neil, L; McGuinness, C; Cao, Y; Su, CH; Nightingale, R; Gdak, K; Mason, G; Grinsell, D; Farrow, H; Ngan, N; Liong, S; Wu, J; McLucas, S; Schedin, P; Junnila, A; Poutanen, M; Haynes, NM; Huntington, ND; Chopin, M; Gebhardt, T; Pal, B; Utzschneider, DT; Mariadason, JM; Kallies, A; Britt, KL; Vasanthakumar, A

Author(s): Hussain, T; Pereira, M; Chisanga, D; Dawson, CA; Tang, A; Thilakasiri, P; Singh, J; Ruppert, M; Davey, A; Man, K; Murer, P; Neil, L; McGuinness, C; Cao, Y; Su, CH; Nightingale, R; Gdak, K; Mason, G; Grinsell, D; Farrow, H; Ngan, N; Liong, S; Wu, J; McLucas, S; Schedin, P; Junnila, A; Poutanen, M; Haynes, NM; Huntington, ND; Chopin, M; Gebhardt, T; Pal, B; Utzschneider, DT; Mariadason, JM; Kallies, A; Britt, KL; Vasanthakumar, A;
Details: Publication Year 2026-08,Volume 27,Issue #8,Page 1737-1748
Journal Title: Nature Immunology
Abstract: Women who have full-term pregnancies have a reduced risk of breast cancer, although the underlying mechanisms are not well understood. Here we show that tissue-resident memory-like T (T(RM)-like) cells are enriched in the breasts of parous women and mice compared to nulliparous individuals. These cells develop during mid-gestation, persist after lactation and are closely associated with mammary epithelial cells, suggesting dependence on epithelial-derived signals. Impaired alveolar differentiation or a deficiency in epithelial cell-derived cytokines interleukin (IL)-15 and transforming growth factor (TGF)beta diminished the expansion of mammary T(RM)-like cells. Single-cell transcriptomics revealed the expanded T(RM)-like cells were heterogeneous, comprising CD8alphabeta(+) and CD8alphaalpha(+) subsets. Lineage tracing showed that these T(RM)-like cells acquire effector functions and contribute to tumor control. Depletion of T(RM)-like cells abrogated breast tumor protection in parous mice, while enhanced IL-2Rbeta signaling-induced T(RM)-like cells and conferred protection in nulliparous mice. Together, we show a mechanism by which pregnancy can induce anticipatory breast cancer protection in a tissue-specific manner.
Publisher: Springer Nature
Keywords: Female; Animals; Pregnancy; Mice; Humans; *Breast Neoplasms/immunology/pathology; *Immunologic Memory; *Memory T Cells/immunology/metabolism; Transforming Growth Factor beta/metabolism; Interleukin-15/metabolism; *CD8-Positive T-Lymphocytes/immunology; Signal Transduction; Mammary Glands, Animal/immunology; Epithelial Cells/immunology; Mice, Inbred C57BL; Parity
Research Division(s): Immunology; Structural Biology
PubMed ID: 42399697
Publisher's Version: https://doi.org/10.1038/s41590-026-02579-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-07-09 08:59:09

Last Modified: 2026-08-14 11:30:41