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Adult survivors of cancer are at increased risk of cardiovascular disease (CVD). Indeed, while CVD emerges as the second leading cause of death in recovering cancer patients, cross-disease communication remains poorly understood. We previously demonstrated that myocardial infarction (MI) accelerates breast cancer tumor growth and cancer-specific mortality in mice and humans. However, whether MI alters tumor growth of other cancer types and impacts metastasis is not known. To assess these gaps, we examined the effect of acute MI, induced by ligation of the left anterior descending (LAD) coronary artery, in syngeneic C57BL6 mouse models of primary and metastatic melanoma. Compared to sham surgery, LAD ligation resulted in a two-fold increase in tumor growth in both the B16 and YUMM melanoma models. Notably, tumor burden significantly correlated with the size of the infarct, suggesting a direct relationship between injury signal activation and disease progression. Analysis of the intratumoral immune cell landscape by flow cytometry revealed an enrichment of immunosuppressive CD4 + FoxP3 + T regulatory cells after MI, and systemic depletion of FoxP3 + cells attenuated MI-induced tumor growth. Finally, histological analysis and magnetic resonance imaging revealed an increase in the number and size of metastatic foci in the liver after MI compared to sham. Our data suggest that MI dampens antitumor immunity and reorganizes the tumor microenvironment to exacerbate tumor progression via infiltration of immunosuppressive FoxP3 + T cells. Collectively, these findings of deleterious cross-disease communication underscore the importance of implementing strategies that mitigate CVD risk in cancer patients.
Itter et al. (Wed,) studied this question.