A new study published in Immunity reveals a key mechanism that allows triple-negative breast cancer (TNBC) to resist treatment. Researchers at Baylor College of Medicine discovered that lipid accumulation in tumor and immune cells promotes immune suppression. However, disrupting lipid formation can reverse treatment resistance and restore an immune-friendly environment.
Lipid Droplets Fuel Resistance to Therapy
TNBC treatment typically involves chemotherapy and immunotherapy, but some tumors that initially respond later develop resistance. Using mouse models, researchers found that TNBC cells that survived treatment accumulated lipid droplets rich in Omega-6 fatty acids. Single-cell RNA sequencing showed that nearby neutrophils, a type of white blood cell, also absorbed these lipids.
Tumor Cells Manipulate Immune Cells
First author Dr. Liqun Yu, a postdoctoral fellow in the Zhang lab at Baylor, explained, “We found that tumor cells transfer lipid droplets to surrounding neutrophils. This process shifts neutrophils from fighting cancer to supporting tumor growth.”
Fatty Acids Trigger Immune Suppression
As reported by medicalxpress, Dr. Xiang H.-F. Zhang, the study’s corresponding author and director of the Lester and Sue Smith Breast Center at Baylor, highlighted the broader implications of fatty acid metabolism in cancer treatment. “Our field has largely focused on how fatty acid metabolism fuels cancer growth. This study reveals that fatty acids also serve as precursors for immunosuppressive signals, allowing cancer cells to evade the immune system.”
Blocking Lipid Accumulation Restores Treatment Effectiveness
By disrupting lipid droplet formation, researchers successfully reversed therapy resistance and the tumor’s ability to suppress the immune system. Additionally, reducing dietary Omega-6 fatty acids resensitized tumors to chemotherapy and immunotherapy.
Implications for Patients and Future Treatments
Dr. Zhang emphasized that dietary adjustments could support treatment. “Patients can follow a diet low in Omega-6 fatty acids, which aligns with general health recommendations to reduce red meat, fat, and sodium intake.” Researchers are also investigating new therapies to block fatty acid accumulation and disrupt immunosuppressive signals between cancer cells and neutrophils.
This breakthrough offers promising strategies to enhance TNBC treatment and overcome therapy resistance.