Positive Pelvic Lymph Nodes in Prostate Cancer Harbor Immune Suppressor Cells To Impair Tumor-reactive T Cells.

UNLABELLED

The impact of prostate cancer (PCa) metastases on pelvic lymph nodes in local antitumor immunity remains unknown. We prospectively enrolled ten hormone therapy-naïve men undergoing salvage pelvic lymph node dissection (sPLND) and analyzed their peripheral blood (PB) and positive pelvic lymph nodes (PPLNs) with PCa metastases for tumor-reactive CD8 T cells and myeloid-derived suppressor cells (MDSCs) using flow cytometry. MDSCs were stratified into CD14 monocytic and CD14 granulocytic types. PD-L1/2 expression was also analyzed for MDSCs. Relative to PB, tumor-reactive CD8 T cells accumulated in PPLNs (p<0.01) yet had decreased proliferation, with low Ki67 expression (p<0.05). Both CD14 monocytic and CD14 granulocytic MDSCs were found in PPLNs, but there was an increase in the proportion of CD8 T cells in PPLNs compared to PB (p<0.01). The granulocytic MDSCs exhibited a high degree of immunosuppressive activity (as evidenced by high pSTAT3 levels) and high levels of B7-H1 (PD-L1) and B7-DC (PD-L2) expression. Thus, granulocytic MDSCs probably suppress tumor-reactive CD8 T-cells in PPLNs and exhibit high expression of immune checkpoint molecules in PCa nodal metastases. The data suggest a relative immunosuppressive state in PPLNs. This provides a biologic rationale for sPLND beyond just tumor debulking, and calls for further investigation of immune checkpoint blockade.

PATIENT SUMMARY

Prostate cancer metastases to lymph nodes may involve immunosuppressive cells that evade antitumor T-cells and create a relatively immunosuppressed state. This provides a rationale for treatment of such lymph nodes and/or for potential immunotherapy.