Polymorphonuclear MDSCs are enriched in the stroma and expanded in metastases of prostate cancer

Jiling Wen1,2, Gang Huang1,2, Sheng Liu3

  • 1Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China.

Insights

Myeloid-derived suppressor cells with polymorphonuclear morphology (PMN-MDSCs) primarily infiltrate the stroma, not the epithelium, in prostate cancer. This stromal enrichment of PMN-MDSCs is more pronounced in metastases, suggesting their role in cancer progression.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Myeloid-derived suppressor cells with polymorphonuclear morphology (PMN-MDSCs) are implicated in prostate cancer progression and immune evasion.
  • The spatial distribution of PMN-MDSCs within tumor compartments (epithelial vs. stromal) in primary and metastatic prostate cancer remains poorly understood.

Purpose of the Study:

  • To characterize the spatial distribution of tumor-infiltrating PMN-MDSCs in primary and metastatic prostate cancer.
  • To compare PMN-MDSC infiltration in epithelial and stromal compartments of prostate tumors.
  • To investigate associations of stromal PMN-MDSCs with clinicopathological features in primary tumors.

Main Methods:

  • A multicolor immunofluorescence staining study was conducted on archived samples.
  • 90 primary prostate tumors, 37 matched lymph node metastases, and 35 bone metastases were analyzed.
  • PMN-MDSCs were identified as CD11b+ CD15+ cells, and prostate epithelial cells as pan-cytokeratin+ cells.

Main Results:

  • PMN-MDSCs were found to infiltrate the stromal compartment more readily than the epithelial compartment in both primary tumors and metastases.
  • Stromal PMN-MDSC infiltration was significantly higher in lymph node and bone metastases compared to primary tumors.
  • In primary tumors, stromal PMN-MDSCs correlated with vascularization, segmented neutrophils, patient age, and proximity to neoplastic epithelial cells.

Conclusions:

  • The tumor stroma, rather than the epithelia, serves as the primary niche for PMN-MDSCs in prostate cancer.
  • These findings support the role of PMN-MDSCs in the metastatic progression of prostate cancer.