纽约大学医学院Kathryn J. Moore研究组发现，心肌梗塞通过先天免疫重编程加速乳腺癌发展。2020年7月13日出版的《自然-医学》发表了该研究成果。

研究人员发现心肌梗塞（MI）会加快小鼠和人乳腺癌细胞的生长以及增加特定于癌症的死亡率。在乳腺癌小鼠模型中，MI通过表观遗传调控将骨髓库中的Ly6C^hi单核细胞重编程产生一种免疫抑制表型，该表型在循环和肿瘤细胞中均保持其在单核细胞的转录水平。同时，MI增加了循环Ly6C^hi单核细胞的水平，并被招募至肿瘤中，这些细胞的缺失消除了MI诱导的肿瘤生长。

此外，在癌症确诊后发生心血管不良事件的早期乳腺癌患者其复发和癌症特异性死亡风险增加。这些临床前和临床结果均表明，MI引起机体内稳态的改变，导致跨疾病交流，从而加速乳腺癌的发展。

据悉，慢性或急性应激源（例如肥胖症或手术）破坏体内稳态会改变癌症的发病机理。由于治疗毒性和生活方式的改变，癌症患者，尤其是乳腺癌患者，患心血管疾病的风险可能会增加。尽管已经确定乳腺癌中心血管不良事件发生的高风险和高发生率，但是尚不清楚此类事件是否影响癌症的发病机理。

附：英文原文

Title: Myocardial infarction accelerates breast cancer via innate immune reprogramming

Author: Graeme J. Koelwyn, Alexandra A. C. Newman, Milessa S. Afonso, Coen van Solingen, Emma M. Corr, Emily J. Brown, Kathleen B. Albers, Naoko Yamaguchi, Deven Narke, Martin Schlegel, Monika Sharma, Lianne C. Shanley, Tessa J. Barrett, Karishma Rahman, Valeria Mezzano, Edward A. Fisher, David S. Park, Jonathan D. Newman, Daniela F. Quail, Erik R. Nelson, Bette J. Caan, Lee W. Jones, Kathryn J. Moore

Issue&Volume: 2020-07-13

Abstract: Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3,4,5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6Chi monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6Chi monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.

DOI: 10.1038/s41591-020-0964-7

Source: https://www.nature.com/articles/s41591-020-0964-7