Metformin: Intratumoral Immune Infiltrates Impact Breast Cancer

Constantinos Savva, MD, MSc, PGDip, MRCP, SCE from the University of Southampton spoke with OncologyTube on Metformin: How Does Its Association with Increased Intratumoral Immune Infiltrates Impact Breast Cancer?


Constantinos Savva, MD, M.Sc., PGDip, MRCP, SCE, from the University of Southampton conducted a study on the effects of metformin, a commonly used diabetes medication, on the immune cell composition within breast cancer tumors. 

The study aimed to investigate whether metformin could modulate immune cell dysfunction caused by chronic inflammation in breast cancer patients.

The researchers conducted two separate peri-surgical window studies, one in Dundee (with 29 patients) and another in Oxford (with 31 patients). 

They analyzed tissue samples using immunohistochemistry to identify specific immune cell markers before and after metformin treatment. 

The densities of immune cell infiltrates were quantified using Definiens Architect software and correlated with clinical parameters.

The results of the study showed that metformin treatment was associated with significant changes in the composition of intratumoral (within the tumor) immune cells.

In both cohorts, metformin was found to increase the density of CD68+ macrophages (a type of immune cell) by 2.5-fold and CD8+ T-cells (another type of immune cell) by 2.7-fold. 

Additionally, metformin led to a decrease in the density of regulatory T-cells (Tregs) by 0.5-fold. 

These changes were observed specifically within the tumor islands and not in the surrounding stroma.

Further analysis stratified by body mass index (BMI) revealed that the effects of metformin on immune cell densities were more pronounced in patients with a high BMI. 

In patients with a healthy BMI, there was no significant difference observed. 

Linear regression analysis confirmed that metformin was independently associated with increased density of CD8+ T-cells.

In the Oxford cohort, the researchers found that patients with high baseline levels of systemic inflammation, indicated by elevated serum leptin, had impaired correlations between certain immune cell subsets. 

However, these correlations were restored after metformin treatment.

The findings of this study suggest that metformin treatment is associated with changes in intratumoral immune cell populations in breast cancer patients. 

The results highlight the potential of metformin as an adjunct therapy to modulate the tumor immune microenvironment.

Further research is needed to explore the potential combination of metformin with immunotherapy in breast cancer treatment.