Macrophage Activation in Dormant and Recurrent Breast Tumors

Abstract

Over 240,000 new breast cancer cases were estimated to be diagnosed cases in 2016. Beyond this, an estimated 40,000 deaths were due to breast cancer last year. Of these deaths, over half are due to recurrence of the disease 5 or more years after initial regression. Despite this, very little is known about the mechanisms behind cancer dormancy or recurrence. Using a doxycycline (dox)-inducible mouse model capable of inducing mammary gland-specific expression HER2 (a commonly overexpressed oncogene in many breast tumors), our lab has shown that macrophages associate with tumor legions throughout all stages of cancer progression, from the primary tumor, through dormancy, and into recurrence. This paper looked to elucidate the role these immune cells are playing in promoting tumor survival and subsequent regrowth by characterizing their activation. We hypothesized that signaling from breast cancer cells causes macrophages to polarize to their pro-tumorigenic, M2 state, which are anti-inflammatory and attenuate adaptive immune responses. Cultured media and co- culture experiments showed an upregulation of IL-10, an M2-specific marker, in macrophages exposed to signaling from both dormant and recurrent tumor cells. These results set the stage for further determining the effects macrophages have on tumor recurrence. Further research into the dynamics between M2 macrophages and dormant cancer cells will help us learn about why and how tumors are able to recur, and will lead to more effective long-term treatments in the future.