Khair Lyne, Hayes Katherine, Tutto Amanda, Samant Amruta, Ferreira Lindsay, Nguyen Tammy T, Brehm Michael, Messina Louis M
Department of Surgery, Division of Vascular Surgery, UMass Memorial Medical Center.
Diabetes Center of Excellence, UMass Chan Medical School.
bioRxiv. 2023 Oct 2:2023.09.30.560299. doi: 10.1101/2023.09.30.560299.
Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.
体育活动是一种可改变的生活方式因素，与降低患乳腺癌的风险相关。虽然体育活动降低癌症风险的确切机制在很大程度上尚不清楚，但据推测，癌症风险的生物学降低是由运动带来的炎症和免疫功能改善所驱动的。造血干细胞（HSCs）是免疫系统所有细胞的祖细胞，通过分化为细胞毒性细胞群体参与癌症免疫监视。在本研究中，我们随着时间推移研究体育活动（PA）在自发发生的乳腺癌模型中的作用，重点关注肿瘤发生率、循环和肿瘤浸润免疫细胞以及肿瘤和造血干细胞的基因表达谱。此外，我们表明，除了PA对荷瘤小鼠免疫细胞的直接作用外，PA还降低了野生型和荷瘤小鼠造血干细胞中的氧化应激，并通过这样做改变造血干细胞向T细胞的分化，以增强癌症免疫监视。
