CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages

The microenvironment of postpartum mammary gland promotes tumor growth and metastasis in animal models and is linked to increased risk of breast cancer and poor disease outcome in patients. Our previous studies showed the involvement of the chemokine CCL8 in breast cancer metastasis through modulation of the tumor-promoting activity of the tumor microenvironment. Here we show that CCL8 is highly expressed during mammary gland involution and enhances the infiltration of M2 subtype macrophages at the second phase of involution. Cancer cell inoculation studies in Ccl8-deficient animals indicate that CCL8 accelerates tumor onset during involution but not in nulliparous animals. Depletion of macrophages abolished the tumor-promoting effect of CCL8 in involution suggesting the specific role of CCL8 in promoting tumor growth by recruiting macrophages. These results underscore the role of CCL8 in the development of postpartum breast cancer and suggest the potential value of targeting CCL8 in disease management.