Men of African descent experience a disproportionately high prostate cancer mortality. We and others have shown that prostate tumors in African-Americans harbor a distinct immuneinflammation signature. Low-grade inflammation has been described as a prostate cancer risk factor that is associated with aggressive disease. We also reported that regular aspirin use reduces the risk of aggressive prostate cancer and disease recurrence in these men. Together, the observations suggest that a low-grade chronic inflammation related to ancestral factors and tumor biology could be a driver of prostate cancer mortality in men with African ancestry.