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

Authors

Tabinda Hussain, Melrine Pereira, David Chisanga, Caleb A Dawson, Adelynn Tang, Pathum Thilakasiri, Jayendra Singh, Meagan Ruppert, Ashleigh Davey, Kevin Man, Patrizia Murer, Liam Neil, Conor McGuinness, Yuxi Cao, Chun-Hsi Su, Rebecca Nightingale, Katie Gdak, Genevieve Mason, Damien Grinsell, Hamish Farrow, Natalie Ngan, Stephanie Liong, Jian Wu, Sarah McLucas, Pepper Schedin, Arttu Junnila, Matti Poutanen, Nicole M Haynes, Nicholas D Huntington, Michael Chopin, Thomas Gebhardt, Bhupinder Pal, Daniel T Utzschneider, John M Mariadason, Axel Kallies, Kara L Britt, Ajithkumar Vasanthakumar

Published in

Nature immunology. Jul 03, 2026. Epub Jul 03, 2026.

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)β diminished the expansion of mammary T_RM-like cells. Single-cell transcriptomics revealed the expanded T_RM-like cells were heterogeneous, comprising CD8αβ⁺ and CD8αα⁺ 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-2Rβ 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.

PMID:
42399697
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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