Higher BMI in Adulthood May Limit the Immune System’s Ability to Fight Breast Cancer

Increased body mass index (BMI) in adulthood may affect a the ability of a patient’s immune system to fight breast cancer cells, according to recent research.

In a recent population-based, prospective study, researchers emphasized the importance of delving further into how lifestyle choices may help the body’s immune system to be better equipped against cancer.

“We have a growing understanding that the body’s immune system plays a central role in both the control and elimination of cancer,” said Dr. Daniel Stover, lead study author, in an interview with CURE®. “This has been known for quite some time, but recent advances harnessing the immune system to help cancer treatments work better have really advanced our knowledge of how important the immune system really is.”

Stover, who is an assistant professor of medical oncology and biomedical informatics at The Ohio State University Comprehensive Cancer Center, added that while efforts to understand how the immune system works — or doesn’t work — against cancer have typically focused on features of the tumor cells themselves, including specific mutations or proteins.

“But there hasn't been as much work done on the host factors or individual factors that might influence the immune system, like a patient's diet, how active they are, what their body composition is,” he explained. “So, we were really interested to try to understand further whether modifiable factors like body composition, physical activity and inflammatory diet might be associated with the immune cells that are around breast cancer cells.”

To measure these factors, Stover and fellow researchers evaluated 882 patients who enrolled in the Nurses’ Health Study (NHS) and the NHS II who were diagnosed with invasive breast cancer with detailed exposure and gene expression data.

Some of the patients (262) had breast tumor immunohistochemistry (IHC) for immune cell markers CD8, CD4, CD20 or CD163. Among these women, the researchers calculated 105 immune cell-specific gene expression signatures. Lasso regression — an analysis method — was used to create immune cell-specific scores based on association with IHC.

The researchers assessed data from the rest of the patients (620) by evaluating each immune-cell specific score as outcomes, using BMI change since age 18, physical activity and dietary inflammatory pattern as predictors for the analysis.

There was a correlation between novel immune cell-specific expression scores and IHC. They also found that BMI change since 18 was positively associated with CD4+ and CD163+ scores. Physical activity and inflammatory dietary patterns were not significantly associated with any immune cell-specific expression score.

Stover said that the reason for lack of significance of physical activity and dietary patterns could be because these factors may have more short-term effects, and that BMI could reflect them integrated together over time. Additionally, the researchers examined one population, whereas other associations may exist in other settings.

“We've known for some time that having a generally healthy approach to life — eating well, staying active — reduces the risk of breast cancer and also reduces the risk of breast cancer recurrence,” Stover said. “Our research suggests that it's possible that some of those factors may also influence the types of immune cells that are found around breast cancers and that may be associated with how our breast cancer treatments work.”

He also explained that the data is early and still needs to be validated in further research to determine whether patients can make lifestyle changes that will impact the immune cells in breast cancer and other cancer types, too.

“I think the next thing is to see whether changes in BMI might also be associated with changes in the immune cells around breast cancer samples or patients that perhaps started with a higher BMI and lost weight or had a decrease, did that also influence (it)?” Stover said. “And I think the other big takeaway from this is that we need to probably dedicate more resources, time and effort to understanding patient factors and modifiable factors that might influence the immune cells in and around breast cancer.”

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