Cell Line-Dependent Internalization, Persistence, and Immunomodulatory Effects of Staphylococcus aureus in...

Area of Science:

• Microbiology
• Immunology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
• Immune checkpoint inhibitors (ICIs) show inconsistent efficacy in TNBC.
• Tumor-associated bacteria may influence immunotherapy outcomes.

Purpose of the Study:

• Investigate Staphylococcus aureus invasion and intracellular persistence in TNBC cells.
• Determine if S. aureus modulates PD-L1 expression in TNBC.
• Explore the role of bacterial infection in TNBC immune signaling.

Main Methods:

• Assessed bacterial uptake and persistence using flow cytometry, gentamicin protection assays, CFU quantification, and electron microscopy.
• Evaluated PD-L1, TLR2, and STAT1 activation after S. aureus infection or TLR2 ligand treatment ± IFN-γ.
• Utilized six TNBC cell lines and one non-tumorigenic control.

Main Results:

• S. aureus was internalized by TNBC cells, with high-uptake lines showing significant cytotoxicity and reduced proliferation.
• Bacterial persistence varied, lasting over 7 days in some TNBC lines.
• IFN-γ combined with S. aureus significantly amplified PD-L1 expression in high-uptake TNBC cells via a TLR2/STAT1 axis.

Conclusions:

• S. aureus invades and persists within TNBC cells, modulating immune signaling pathways.
• Bacterial presence influences PD-L1 expression, a key immune checkpoint target.
• Targeting tumor-bacteria interactions presents a potential novel strategy to improve immunotherapy efficacy in TNBC.