澳大利亚墨尔本大学Sherene Loi小组在研究中取得进展。他们的论文发现了分娩和哺乳期诱导T细胞介导的乳腺癌保护。2025年10月20日出版的《自然》杂志发表了这项成果。

研究团队发现胎次诱导CD8⁺ T细胞的积累，包括人类正常乳腺组织中具有组织驻留记忆（TRM）样表型的细胞。在小鼠模型中，怀孕后的哺乳期和复复期驱动CD8乳腺中的T细胞，与肿瘤生长减少和瘤内免疫细胞浸润增加相一致，这些作用被CD8T细胞耗竭。重要的是，这种依赖CD8⁺ T细胞的肿瘤控制仅在哺乳和复归的完整周期后观察到。与此一致的是，来自幼年妇女的原发性TNBCs表现出更大的T细胞浸润和改善的临床结果。这些发现跨越临床前模型和超过1000例患者样本，为生殖史如何影响乳房免疫、定位CD8T细胞作为生育相关保护的关键介质，并为预防和治疗乳腺癌提供新策略。

据悉，胎次和母乳喂养可降低乳腺癌的风险，特别是三阴性乳腺癌（TNBC），但这种保护作用背后的免疫学机制尚不清楚。

附：英文原文

Title: Parity and lactation induce T cell mediated breast cancer protection

Author: Virassamy, Balaji, Caramia, Franco, Savas, Peter, Harris, Michael A., Pan, Jia-Wern, Wang, Jianan, Brown, Emmaline, OMalley, Megan M. R., van Geelen, Courtney T., Hun, Michael, Burn, Thomas N., Sant, Sneha, Ballan, Jamieson D., Kay, Jasmine, Lara Gonzalez, Luis E., Clarke, Kylie, Aw Yeang, Han Xian, Idrizi, Rejhan, Jana, Metta, Challice, Damon J., Salgado, Roberto, Thorne, Heather, Poliness, Cathie, Nightingale, Sophie, Teo, Soo-Hwang, Speed, Terence P., Visvader, Jane, Neeson, Paul J., Darcy, Phillip K., Mackay, Laura K., Loi, Sherene

Issue&Volume: 2025-10-20

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 (TRM)-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.

DOI: 10.1038/s41586-025-09713-5

Source: https://www.nature.com/articles/s41586-025-09713-5