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

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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. 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.

Original languageEnglish (US)
JournalEuropean Urology Focus
DOIs
StateAccepted/In press - 2016

Fingerprint

Prostatic Neoplasms
Lymph Nodes
T-Lymphocytes
Neoplasms
Immunosuppressive Agents
Neoplasm Metastasis
Lymph Node Excision
Immunotherapy
Myeloid-Derived Suppressor Cells
Immunity
Flow Cytometry
Therapeutics
Hormones

Keywords

  • Immune checkpoint blockade
  • Immuno-oncology
  • Prostate cancer
  • Salvage lymphadenectomy

ASJC Scopus subject areas

  • Urology

Cite this

@article{41c15fa4f403401a9b0db09e9a2ebc22,
title = "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-na{\"i}ve 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.",
keywords = "Immune checkpoint blockade, Immuno-oncology, Prostate cancer, Salvage lymphadenectomy",
author = "Vidit Sharma and Dong, {Haidong M} and Kwon, {Eugene D} and Karnes, {Robert Jeffrey}",
year = "2016",
doi = "10.1016/j.euf.2016.09.003",
language = "English (US)",
journal = "European Urology Focus",
issn = "2405-4569",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Positive Pelvic Lymph Nodes in Prostate Cancer Harbor Immune Suppressor Cells To Impair Tumor-reactive T Cells

AU - Sharma, Vidit

AU - Dong, Haidong M

AU - Kwon, Eugene D

AU - Karnes, Robert Jeffrey

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Immune checkpoint blockade

KW - Immuno-oncology

KW - Prostate cancer

KW - Salvage lymphadenectomy

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