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

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. In this study, we found data suggesting a relative immunosuppressive state in positive pelvic lymph nodes. This provides a biologic rationale for metastasis-directed therapy beyond just tumor debulking and also calls for further investigation of immune checkpoint blockade.