How Tumor-Immune Cell Clusters Influence Breast Cancer Metastasis

Recent research from Northwestern University has shed light on the mechanisms driving the spread of breast cancer, emphasizing the critical role of cellular interactions in the bloodstream. In two comprehensive studies published in Nature Communications and The Journal of Clinical Investigation, scientists explored how circulating tumor cells (CTCs) form clusters with immune cells, significantly increasing their metastatic potential.

The first study identified the protein Plexin-B2 (PLXNB2) as a key factor in tumor cell clustering. Using computational algorithms, researchers found that PLXNB2 is highly expressed in multicellular CTC clusters, which are up to fifty times more efficient at establishing metastases compared to individual tumor cells. Liu, the lead researcher, explained that tumor cells traveling through the bloodstream can encounter physical and immune system hurdles. By associating with immune cells, these clusters can evade immune surveillance and enhance their ability to seed new tumors. Mouse experiments demonstrated that disrupting PLXNB2 reduced lung metastases, suggesting it could be a promising therapeutic target.

The second study focused on the immune landscape within circulating tumor clusters. Analysis of blood samples from advanced breast cancer patients revealed that over 75% of samples contained such clusters, which included rare T-cells—specifically double-positive CD4/CD8 T-cells (DPTs). These cells exhibited immunosuppressive traits, aiding tumor evasion. Researchers identified two molecules, VLA-4 on DPT cells and VCAM-1 on tumor cells, that facilitate cluster formation. Blocking this interaction in mice significantly impeded clustering and improved survival outcomes.

These groundbreaking findings highlight the dual roles of tumor cell properties and immune interactions in metastasis. Targeting key proteins like PLXNB2, or blocking the VLA-4/VCAM-1 interaction, holds potential for preventing the spread of breast cancer at early stages. This research enhances our understanding of cancer biology, revealing new avenues for therapy that could inhibit metastasis, thereby improving patient prognosis.

Source: [https://medicalxpress.com/news/2025-09-tumor-immune-cell-clusters-breast.html]