Recent research has revealed that pregnancy and breastfeeding generate long-lasting CD8+ T lymphocytes that remain active in breast tissue, offering enduring immune protection. This groundbreaking discovery, described by scientists as a "paradigm shift," was unveiled at the 2025 European Society for Medical Oncology (ESMO) Annual Meeting in Berlin and published simultaneaously in Nature. The findings have the potential to reshap how sceintistws and clinicians understand breast cancer (BC) prevention and treatment, especially regarding immune-related mechanisms in women's health.
For decades, it has been known that women who experience pregnancy and breastfeeding face a lower risk of developing breast cancer, particularly the highly aggressive triple-negative subtype (TNBC). However, the biological explanation behind this protective effect remained unclear. According to Professor Sherene Loi, a breast cancer oncologist at the Peter MacCallum Cancer Centre in Melbourne previous theories largely attributed this reduce risk to hormonal and structural changes that occur in breast tissue after pregnancy and lactation. Loi and her team set out to determine whether immune factors might also play a significant role in this phenomenon.
To explore this question, the researchers examined normal breast tissue samples from more than 250 women who had undergone breast reduction or preventive mastectomy surgeries. These participants represented diverse ethnic backgrounds, including African, American, European, and Asian populations. Using advanced technologies such as single-cell RNA sequencing, flow cytometry, and multiplex imaging, the team analyzed the presence and characteristics of CD*+ T cells within the breast tissue and how these immune profiles correlated with clinical outcomes.
Their investigations revealed a striking difference between women who had given birth and those who had never been pregnant. Tissues from women with a history of pregnancy contained significantly higher numbers of CD8+ T lymphocytes, particularly long-lived tissue-resident memory cells. These immune cells appeared to persist in the breast for decades after childbirth, suggesting that pregnancy leaves behind a durable immune imprint that enhances local immune surveillance and protection against malignancy.
Supporting experiments in mouse models confirmed these findings. Mice that underwent a full reproductive cycle, pregnancy, breastfeeding, and breast involution, developed an enriched pool of mammary CD8+ T cells. These mice showed strong resistance to tumor growth, especially from triple-negative breast cancer cells. When scientists depleted the CD8+ T cells experimentally, the protective effect disappeared, confirming the central role of these immune cells. Similarly, human data showed that women who had breastfed and been pregnant displayed higher CD8+ T-cell densities within tumors and improved survival rates in early-stage TNBC.
The study’s implications extend beyond reproductive health. It suggests that reproductive history may influence lifelong immunity in breast tissue, redefining how clinicians assess cancer risk and prevention strategies. Professor Loi emphasized that immunity should not only be viewed as a target for treatment but also as a key determinant of cancer susceptibility. This discovery opens potential pathways for immune-based preventive approaches and for optimizing immunotherapy in breast cancer management. The research, supported by leading health organizations and institutions, marks a major advance in the understanding of how natural life events like pregnancy can shape immune resilience and influence long-term cancer outcomes.
