Myocardial infarction accelerates breast cancer via innate immune reprogramming

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. NelsonBette J. Caan, Lee W. Jones, Kathryn J. Moore

Research output: Contribution to journalArticlepeer-review

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 behaviors3–5. 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.

Original languageEnglish (US)
Pages (from-to)1452-1458
Number of pages7
JournalNature Medicine
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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