Triple-negative breast cancer is a type of breast cancer that is particularly aggressive and often fatal due to limited treatment options and a high likelihood of recurrence.
Researchers have recently discovered that breast cancer stem cells evade the immune system by coordinating changes in their differentiation and metabolism (Figure 1). Specifically, the stem cells downregulate the mevalonate pathway, a metabolic pathway that leads to the production of molecules that gamma delta T cells can recognize.
Gamma delta T cells are a type of immune cell that can recognize and kill cells that produce stress-induced molecules and phosphoantigens, which are common characteristics of cancer cells.
While gamma delta T cells have been proposed as a potential immunotherapy for triple-negative breast cancer, the researchers found that the cancer cells’ adaptations make them less effective in a mouse model. However, the researchers discovered that zolendronate, a drug used to treat osteoporosis and bone metastasis, can counteract the metabolic change in the cancer cells and make gamma delta T cells more efficient at clearing the cancer cells. The findings suggest that zolendronate could be a promising approach to enhance the efficacy of gamma delta T cells against triple-negative breast cancer and to develop novel combinatorial immunotherapies.
Journal article: Raute, K., et al., 2023. Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands. Cancer Immunology Research.
Summary by Stefan Botha