肿瘤浸润和循环粒细胞髓源抑制细胞与蕈样肉芽肿病的疾病活动和不良临床结局相关。
Tumor-infiltrating and circulating granulocytic myeloid-derived suppressor cells correlate with disease activity and adverse clinical outcomes in mycosis fungoides.
机构信息
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hematology Department, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
出版信息
Clin Transl Oncol. 2020 Jul;22(7):1059-1066. doi: 10.1007/s12094-019-02231-7. Epub 2019 Nov 6.
PURPOSE
Cutaneous T cell lymphomas (CTCL) are rare and histologically diverse lymphoproliferative neoplasms, with mycosis fungoides (MF) representing the most common disease subset. Given the emerging role of myeloid-derived suppressor cells (MDSC) as a clinically applicable biomarker in solid tumors, we sought to investigate the presence of tumor-infiltrating and circulating MDSC in early- and advanced-stage MF patients and evaluate their prognostic significance in patient overall survival.
METHODS
Tumor-infiltrating MDSC were assessed immunohistochemically with Arginase-1 in 31 MF and 14 non-MF skin punch biopsies. Circulating MDSC were assessed with flow cytometry in freshly isolated PBMC from 29 MF patients. Granulocytic MDSC (G-MDSC) were defined as CD11b+CD14-CD15+ and monocytic MDSC (M-MDSC) were defined as CD11b+CD14+HLA-DRlow/-.
RESULTS
MDSC infiltration occurred in approximately one-third (35.5%) of CTCL lesions, with a predilection for non-MF lesions (p < 0.05). The predominant morphology of MDSC was granulocytic. Although in MF lesions the presence of MDSC infiltrates did not correlate with clinical stage, it conferred significantly worse overall survival outcomes (p < 0.05). Circulating G-MDSC were significantly higher in MF patients compared to healthy donor controls (p < 0.0001), while M-MDSC did not show any statistically significant difference. G-MDSC were significantly higher in patients with active disease compared to patients who were in partial remission (p < 0.01). As with tumor-infiltrating MDSC, clinical stage did not correlate with circulating G-MDSC levels, while prospective overall survival analysis showed that patients with high levels of circulating G-MDSC have significantly inferior outcomes (p < 0.01).
CONCLUSIONS
This study shows that G-MDSC could represent a novel and easily assessable biomarker in MF, which mirrors disease activity and can predict patient subgroups with aggressive clinical features.
目的
皮肤 T 细胞淋巴瘤（CTCL）是一种罕见的、组织学多样化的淋巴增生性肿瘤，蕈样真菌病（MF）是最常见的疾病亚型。鉴于髓系来源的抑制细胞（MDSC）作为实体瘤中一种具有临床应用价值的生物标志物的作用不断显现，我们试图研究早期和晚期 MF 患者中肿瘤浸润和循环 MDSC 的存在，并评估其对患者总生存的预后意义。
方法
用 Arginase-1 免疫组化法检测 31 例 MF 和 14 例非 MF 皮肤活检标本中的肿瘤浸润 MDSC。用流式细胞术检测 29 例 MF 患者新鲜分离的 PBMC 中的循环 MDSC。粒细胞 MDSC（G-MDSC）定义为 CD11b+CD14-CD15+，单核细胞 MDSC（M-MDSC）定义为 CD11b+CD14+HLA-DRlow/-。
结果
MDSC 浸润约发生在三分之一（35.5%）的 CTCL 病变中，MF 病变中更为常见（p<0.05）。MDSC 的主要形态为粒细胞。尽管在 MF 病变中，MDSC 浸润与临床分期无相关性，但它与总生存结局显著较差相关（p<0.05）。与健康供体对照相比，MF 患者的循环 G-MDSC 显著升高（p<0.0001），而 M-MDSC 无统计学差异。与处于部分缓解的患者相比，处于活动期的患者的循环 G-MDSC 显著升高（p<0.01）。与肿瘤浸润 MDSC 一样，临床分期与循环 G-MDSC 水平不相关，而前瞻性总生存分析显示，高水平循环 G-MDSC 的患者预后显著较差（p<0.01）。
结论
本研究表明，G-MDSC 可能是 MF 中的一种新的、易于评估的生物标志物，它反映了疾病的活动度，并可预测具有侵袭性临床特征的患者亚组。
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