Immunological differences between primary and metastatic breast cancer.

Area of Science:

• Immunology
• Oncology
• Translational Research

Background:

• The immune microenvironment of breast cancer is not well understood during disease progression.
• Investigating changes in immune cell infiltration and molecular markers is crucial for understanding tumor evolution.

Purpose of the Study:

• To compare the immune microenvironment between primary and metastatic breast cancer samples.
• To identify changes in tumor-infiltrating lymphocytes (TILs), programmed death-ligand 1 (PD-L1) expression, and immune-related genes during breast cancer metastasis.

Main Methods:

• Compared TIL count and PD-L1 protein expression via immunohistochemistry in primary and metastatic breast cancer.
• Analyzed mRNA levels of 730 immune-related genes using Nanostring technology.
• Evaluated immune cell metagenes, therapeutic targets, and pathway gene expression.

Main Results:

• Metastatic tumors had significantly lower TIL counts and PD-L1 positivity compared to primary tumors.
• Expression of numerous immune cell markers, immuno-oncology targets (e.g., PD1, CTLA4), and immune-activating pathways (e.g., interferon, MHC class I) were significantly downregulated in metastases.
• Macrophage markers, protumorigenic pathways (e.g., TLR), and complement receptors remained highly expressed in metastases, indicating potential therapeutic targets.

Conclusions:

• Metastatic breast cancers are immunologically less active than primary tumors.
• Despite reduced immune activity, preserved expression of certain immune-oncology targets and macrophage/angiogenesis signatures suggests potential for combination immunotherapy strategies.
• These findings highlight the need for tailored therapeutic approaches for metastatic breast cancer.