Identification of cycling regulatory T cell precursors as conductors of immune escape during breast carcinoma progression
Menée sur des rats et à l'aide d'échantillons de tissus mammaires sains et d'échantillons tumoraux provenant de patientes atteintes d'un carcinome canalaire in situ ou d'un cancer invasif du sein, cette étude met en évidence le rôle des lymphocytes T régulateurs en phase de prolifération active (cycTreg) dans l'échappement immunitaire qui survient lors de la progression tumorale
Immune escape during the ductal carcinoma in situ (DCIS)-to-invasive breast cancer (IBC) transition shapes tumor evolution. Through transcriptomic mapping of the immune landscapes of normal breast, DCIS, and IBC from large patient cohorts, we identified T and myeloid cells as the primary distinguishing features between DCIS and IBC. We discovered cycling regulatory T cells (cycTreg) as an orchestrator of immunosuppression in IBC. cycTreg frequency predicts cytotoxic CD8+, TCR diversity, disease-specific survival in IBC, and recurrence in DCIS. In a rat model of breast cancer, we demonstrated that cycTreg act as precursors to mature Treg and are inducible by tumor-localized type 2 dendritic cells. Profiling of tumors subjected to αOX40 and αPD-L1 therapies revealed an IL-33-mediated fibroblast-cycTreg signaling loop, the disruption of which enhances intratumoral antigen-experienced CD8+ effectors and systemic immunosurveillance. Our study defines cycTreg as critical inducers of immune escape and promising immuno-oncology targets in breast cancer.
Cancer Cell , article en libre accès, 2026