Myocardial infarction accelerates breast cancer via innate immune reprogramming.
Myocardial infarction accelerates breast cancer via innate immune reprogramming.
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DOI：
10.1038/s41591-020-0964-7
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发表时间：
2020-09
期刊：
影响因子：
82.9
通讯作者：
Moore KJ
中科院分区：
文献类型：
--
作者：
Koelwyn GJ;Newman AAC;Afonso MS;van Solingen C;Corr EM;Brown EJ;Albers KB;Yamaguchi N;Narke D;Schlegel M;Sharma M;Shanley LC;Barrett TJ;Rahman K;Mezzano V;Fisher EA;Park DS;Newman JD;Quail DF;Nelson ER;Caan BJ;Jones LW;Moore KJ
慢性或急性应激源（如肥胖或手术）对系统内稳态的破坏会改变癌症的发病机制。癌症患者，特别是乳腺癌患者，由于治疗毒性和生活方式行为的改变，患心血管疾病的风险可能会增加。虽然乳腺癌中心血管事件的风险和发生率升高是公认的，但这些事件是否影响癌症的发病机制尚不清楚。在这里，我们表明心肌梗死（MI）加速了小鼠和人类乳腺癌的生长和癌症特异性死亡率。在乳腺癌小鼠模型中，MI通过表观遗传将骨髓储存库中的ly6high单核细胞重编程为免疫抑制表型，该表型在循环和肿瘤中的单核细胞中维持在转录水平。同时，心肌梗死增加循环ly6high单核细胞水平和肿瘤募集，这些细胞的消耗消除了心肌梗死诱导的肿瘤生长。此外，在癌症诊断后经历心血管事件的早期乳腺癌患者复发和癌症特异性死亡的风险增加。这些临床前和临床结果表明，心肌梗死诱导全身稳态改变，引发疾病间交流，加速乳腺癌的发生。
Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity or surgery, alters cancer pathogenesis. Cancer patients, particularly those with breast cancer, can be at increased risk for cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors. 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 Ly6Chigh 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 Ly6Chigh monocyte levels and recruitment to tumors, and depletion of these cells abrogated MI-induced tumor growth. Furthermore, early-stage breast cancer patients 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 to systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
Pamer EG
影响因子：
17.1
作者：
Krall JA;Reinhardt F;Mercury OA;Pattabiraman DR;Brooks MW;Dougan M;Lambert AW;Bierie B;Ploegh HL;Dougan SK;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
64.5
作者：
Mitroulis I;Ruppova K;Wang B;Chen LS;Grzybek M;Grinenko T;Eugster A;Troullinaki M;Palladini A;Kourtzelis I;Chatzigeorgiou A;Schlitzer A;Beyer M;Joosten LAB;Isermann B;Lesche M;Petzold A;Simons K;Henry I;Dahl A;Schultze JL;Wielockx B;Zamboni N;Mirtschink P;Coskun Ü;Hajishengallis G;Netea MG;Chavakis T
通讯作者：
Chavakis T
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO