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 language | English (US) |
|---|---|
| Journal | European Urology Focus |
| DOIs | |
| State | Accepted/In press - 2016 |
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Keywords
- Immune checkpoint blockade
- Immuno-oncology
- Prostate cancer
- Salvage lymphadenectomy
ASJC Scopus subject areas
- Urology
Cite this
Positive Pelvic Lymph Nodes in Prostate Cancer Harbor Immune Suppressor Cells To Impair Tumor-reactive T Cells. / Sharma, Vidit; Dong, Haidong M; Kwon, Eugene D; Karnes, Robert Jeffrey.
In: European Urology Focus, 2016.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84994508669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994508669&partnerID=8YFLogxK
U2 - 10.1016/j.euf.2016.09.003
DO - 10.1016/j.euf.2016.09.003
M3 - Article
C2 - 28753790
AN - SCOPUS:84994508669
JO - European Urology Focus
JF - European Urology Focus
SN - 2405-4569
ER -