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

Abstract

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.

• Authors: Vidit Sharma, Haidong Dong, Eugene Kwon, R Jeffrey Karnes
• Journal: European urology focus (Eur Urol Focus) Vol. 4 Issue 1 Pg. 75-79 (01 2018) ISSN: 2405-4569 [Electronic] Netherlands
• PMID: 28753790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Ki-67 Antigen
• MKI67 protein, human

Topics

• Aged
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Flow Cytometry (methods)
• Humans
• Immunotherapy (methods)
• Ki-67 Antigen (immunology)
• Lymph Node Excision (methods)
• Lymph Nodes (immunology, pathology, surgery)
• Male
• Middle Aged
• Myeloid-Derived Suppressor Cells (immunology)
• Neoplasm Metastasis
• Prospective Studies
• Prostatic Neoplasms (immunology, pathology, secondary, surgery)
• Salvage Therapy (methods)