Pregnancy induced TRM cells protect against breast cancer [scRNAseq]

ABSTRACT: Age and parity are well-known factors that influence breast cancer development (1-3). Epidemiological studies have shown that women who have had multiple pregnancies are at a lower risk of developing breast cancer than women who have no history of pregnancy (4, 5). However, mechanisms that link parity and cancer protection are unclear. We discovered that CD8+ T cells with a tissue-resident memory (TRM) phenotype enriched in the mammary glands of parous women and mice compared to their virgin counterparts. Developmental kinetics revealed that these cells seeded the mammary gland during early gestation but persisted post lactation and was specific to the mammary glands. While these CD8 T cells expressed the TRM specific transcription factor Hobit, single cell transcriptomics revealed expansion of transcriptionally distinct canonical and non-canonical TRM populations, including a novel Hobit+ innate T cells (ITCs) in the parous mammary gland compared to their virgin counterparts. Furthermore, imaging analysis uncovered that the TRM like cells were associated with mammary epithelial cells and impairment in mammary gland branching during pregnancy significantly affected their differentiation or population expansion. In keeping with their association with mammary epithelial cells, all TRM subsets, including the Hobit+ITCs commonly required the cytokines TGF-β and IL-15 for their differentiation. Notably, depletion of CD103+ T cells exacerbated tumour growth in parous mice and lineage tracing experiments revealed that the canonical TRM like cells switched to an effector phenotype in tumours and contributed to tumour control. Together, we show for the first time that parity induces novel and heterogenous TRM like populations in the mammary gland that are central in providing protection against breast cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE292733 | GEO | 2026/05/02

REPOSITORIES: GEO