Parity and lactation induce T cell mediated breast cancer protection

Abstract

Parity and breastfeeding reduce the risk of breast cancer, particularly triple-negative breast cancer (TNBC)^1,2, yet the immunological mechanisms underlying this protection remain unclear. Here, we show that parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident memory (T_RM)-like phenotype within human normal breast tissue. In murine models, pregnancy followed by lactation and involution drove the accumulation of CD8⁺ T cells in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune cell infiltration, effects that were abrogated by CD8⁺ T cell depletion. Importantly, this CD8⁺ T cell dependent tumour control was only observed following a complete cycle of lactation and involution. Consistent with this, primary TNBCs from parous women exhibited greater T cell infiltration and improved clinical outcomes. Together these findings, spanning preclinical models and over 1000 patient samples, provide new insight into how reproductive history shapes breast immunity, positioning CD8⁺ T cells as key mediators of parity-associated protection and informing novel strategies for both prevention and treatment of breast cancer.