Pregnancy-Induced Memory-Like T Cells Linked To Breast Tumor Control

03 Jul 20264 min read2 viewsJournal Feed

GIST (Key Takeaways)

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.