Breast cancer microenvironment composition associated with high PD-L1 expression

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Breast cancer (BC) heterogeneity complicates diagnosis, treatment, and prognosis.
• The tumor microenvironment (TME) significantly influences BC development and progression.
• Understanding TME characteristics is crucial for BC management.

Purpose of the Study:

• To characterize the TME in early-stage BC based on PD-L1 expression.
• To analyze immune cell infiltration (CD68+, CD163+, mast cells), cytokine profiles (IL-6, IL-10, TNF-α), and extracellular matrix components (VIM, TGF-β1, COL1A1, COL3A1, MMPs, LOX, PLOD).
• To identify TME features associated with an immunosuppressive and tumor-promoting phenotype.

Main Methods:

• Analysis of postoperative material from 124 patients with stage I-II BC.
• Immunohistochemical analysis of TME markers.
• Real-time RT-PCR for mRNA gene expression.
• ELISA for serum cytokine levels.

Main Results:

• High PD-L1 expression associated with increased CD163+ macrophages (2.9x) and mast cells (2.5x).
• Elevated serum IL-10 and decreased IL-6 in high PD-L1 BC.
• Increased TGF-β1 (2.13x), COL1A1 (13.24%), MMPs (-1, -8, -13, -2, -9), and LOX (2.48x) in high PD-L1 tumors.

Conclusions:

• High PD-L1 expression in BC is linked to an immunosuppressive TME.
• This includes increased infiltration of pro-tumorigenic immune cells.
• Alterations in cytokine profiles and stromal matrix remodeling are associated with high PD-L1 expression in BC.