Department of Urology, Mayo Clinic, Rochester, MN, USA.
Department of Urology, Mayo Clinic, Rochester, MN, USA.
Eur Urol Focus. 2018 Jan;4(1):75-79. doi: 10.1016/j.euf.2016.09.003. Epub 2016 Sep 21.
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.
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.
前列腺癌（PCa）转移对局部抗肿瘤免疫的盆腔淋巴结的影响尚不清楚。我们前瞻性地招募了 10 名接受挽救性盆腔淋巴结清扫术（sPLND）的激素治疗初治男性，并使用流式细胞术分析了他们的外周血（PB）和阳性盆腔淋巴结（PPLN）中具有 PCa 转移的肿瘤反应性 CD8 T 细胞和髓系来源的抑制细胞（MDSCs）。MDSC 分为 CD14 单核细胞和 CD14 粒细胞型。还分析了 MDSC 的 PD-L1/2 表达。与 PB 相比，肿瘤反应性 CD8 T 细胞在 PPLN 中聚集（p<0.01），但增殖减少，Ki67 表达水平较低（p<0.05）。PPLN 中均发现 CD14 单核细胞和 CD14 粒细胞 MDSC，但与 PB 相比，PPLN 中 CD8 T 细胞的比例增加（p<0.01）。粒细胞 MDSC 表现出高度的免疫抑制活性（表现为高 pSTAT3 水平）和高水平的 B7-H1（PD-L1）和 B7-DC（PD-L2）表达。因此，粒细胞 MDSC 可能在 PPLN 中抑制肿瘤反应性 CD8 T 细胞，并在 PCa 淋巴结转移中表现出高免疫检查点分子表达。数据表明 PPLN 中存在相对免疫抑制状态。这为 sPLND 提供了除肿瘤减灭术以外的生物学依据，并呼吁进一步研究免疫检查点阻断。
前列腺癌转移到淋巴结可能涉及逃避抗肿瘤 T 细胞的免疫抑制细胞，并形成相对免疫抑制状态。这为治疗此类淋巴结和/或潜在免疫治疗提供了依据。
