Monocytes Provoke Breast Cancer Cells to Express PD-L1 via a Cell-to-Cell Interaction Involving CD44 and Moesin

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) has a poor prognosis, with limited response rates to current immunotherapies.
• Immune checkpoint inhibitors (ICIs) are used for TNBC, but about half of patients do not respond significantly.
• The role of monocytes in the tumor microenvironment (TME) and their influence on breast cancer cells (BCCs) regarding PD-L1 expression remains unclear.

Purpose of the Study:

• To investigate whether monocytes promote PD-L1 expression in breast cancer cells.
• To elucidate the molecular mechanisms underlying monocyte-induced PD-L1 expression in BCCs.

Main Methods:

• Co-culture of monocytes and breast cancer cells.
• Quantitative PCR to measure PD-L1 mRNA levels.
• RNA sequencing to identify differentially expressed genes.
• siRNA-mediated knockdown of Moesin.
• Blocking experiments using CD44 antibody.

Main Results:

• Co-culture with monocytes significantly increased PD-L1 and its mRNA levels in BCCs.
• RNA sequencing revealed overexpression of Moesin mRNA in BCCs after co-culture.
• Knockdown of Moesin using siRNA reversed the increased PD-L1 expression.
• Addition of CD44 antibody blocked the monocyte-induced PD-L1 upregulation.

Conclusions:

• Monocytes enhance PD-L1 expression in breast cancer cells through a mechanism involving Moesin and CD44-mediated cell-to-cell interaction.
• This Moesin-CD44 pathway represents a novel mechanism of tumor immune evasion in TNBC.
• Findings suggest potential therapeutic strategies to overcome resistance to immune checkpoint blockade therapy in TNBC.