Obesity Reprograms Immune Cells in Mammary Tissues to Promote Tumor Development, Study Says

Obesity in women with triple-negative breast cancer, the most aggressive kind of breast cancer, reprograms immune cells and creates a chronic inflammatory environment that promotes cancer progression and spread, a study has found.

The study, “Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer,” was published in the Journal of Experimental Medicine.

Obesity is one of the major risk factors for the development of breast cancer, accounting for approximately 20% of all cancer-related deaths. Besides increasing overall breast cancer mortality, obesity also seems to increase a woman’s chance of developing the most aggressive forms of breast cancer, including triple-negative breast cancer (TNBC).

Previous studies have shown a strong relationship between obesity and disease progression among women with TNBC. However, the reasons why obesity predisposes these women to a poor prognosis are still unclear.

Obesity has been shown to promote chronic inflammation in fat tissues by promoting the infiltration and activation of certain immune cells.

Therefore, one hypothesis for the strong link between obesity and TNBC progression may be that these immune cells might be doing the same thing in mammary fat tissues, creating an inflammatory environment prone to tumor development.

In this study, a group of researchers from the University of Chicago set out to explore this hypothesis, using a mouse model of induced obesity and TNBC.

To this end, they fed normal female mice with a low- or high-fat diet for a period of 12 weeks, and then injected different types of TNBC malignant cells into the mammary fat pads of lean and obese animals to trigger the development of breast cancer. Tumor development was monitored in all animals for a period of nine weeks while they remained on their respective diets.

Analyses showed that obese female mice had infiltration and overactivation of macrophages — a type of immune cell responsible for removing dead cells and debris from tissues — in their mammary fat pads.

However, these macrophages produced large amounts of interleukin-6 (IL-6), a pro-inflammatory cytokine, that enhanced tumor formation and cancer cells’ stemness (their ability to remain in an undifferentiated and highly proliferative state) in obese animals. A cytokine is a molecule that mediates and regulates immune and inflammatory responses.

The investigators found the same overactivated macrophages in mammary fat tissue samples from obese women who had undergone breast reduction surgery, suggesting that obesity may in fact reprogram these immune cells in such a way that, instead of fighting cancer, they stimulate its formation.

“Our studies, in mice and humans implicate these metabolically-activated adipose [fat] tissue macrophages [in tumor formation and progression],” Lev Becker, PhD, an assistant professor in the Ben May Department for Cancer Research at the University of Chicago and author of the study, said in a news release.

The researchers found that weight loss was able to revert all obesity-induced effects on macrophages’ overactivation and TNBC tumor development in obese female mice that started being fed a low-fat diet, “highlighting the potential therapeutic value of weight loss intervention.”

Therefore, weight loss is important for the obese, the researchers said, not only as a preventive measure to minimize the risk of breast cancer, but also as a therapeutic intervention that may benefit patients even after they’ve been diagnosed.