Journal of the American Academy of Dermatology ( IF 13.8 ) Pub Date : 2017-12-19 , DOI: 10.1016/j.jaad.2017.12.029 Thibault Kervarrec , Pauline Gaboriaud , Patricia Berthon , Julia Zaragoza , David Schrama , Roland Houben , Yannick Le Corre , Ewa Hainaut-Wierzbicka , Francois Aubin , Guido Bens , Jorge Domenech , Serge Guyétant , Antoine Touzé , Mahtab Samimi
Background
Merkel cell carcinoma (MCC) is a rare tumor of the skin that has an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells needs better characterization.
Objective
To characterize tumor-infiltrating myeloid cells in MCC and their association with other immune effectors and patient outcome.
Methods
MCC cases were reviewed from an ongoing prospective cohort study. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils, and myeloid-derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, CD33, and human leukocyte antigen-DR. Associations of these cell populations with programmed cell death ligand 1 expression, CD8 infiltrates, and vascular density were assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model.
Results
The median density of macrophages was 216 cells/mm2. CD68+ and CD33+ macrophage densities were associated with CD8+ T-cell infiltrates and programmed cell death ligand 1 expression. In addition, MCC harboring CD8+ T cell infiltrates and brisk CD33+ myeloid cell infiltrates were significantly and independently associated with improved outcomes (recurrence-free and overall survival).
Limitations
Sampling bias and the retrospective design were potential study limitations.
Conclusion
Infiltration of CD33+ myeloid cells and CD8+ T lymphocytes defines a subset of MCC associated with improved outcome.
中文翻译:
CD33 +髓样细胞和CD8 + T细胞浸润的默克尔细胞癌可改善预后
背景
默克尔细胞癌(MCC)是一种具有侵略性行为的罕见皮肤肿瘤。免疫力是MCC发育的主要调节因子,淋巴细胞和肿瘤细胞之间的许多相互作用已得到证实。然而,肿瘤浸润性髓细胞的影响需要更好的表征。
客观的
表征MCC中肿瘤浸润的髓样细胞及其与其他免疫效应物和患者预后的关系。
方法
一项正在进行的前瞻性队列研究对MCC病例进行了回顾。在组织微阵列中总共包括103个一式三份的肿瘤样品。巨噬细胞,嗜中性粒细胞和髓样来源的抑制细胞的特征在于以下标记:CD68,CD33,CD163,CD15,CD33和人白细胞抗原-DR。评估这些细胞群与程序性细胞死亡配体1表达,CD8浸润和血管密度的关联。通过对数秩检验和Cox多元模型分析对生存的影响。
结果
巨噬细胞的中位密度为216个细胞/ mm 2。CD68 +和CD33 +巨噬细胞密度与CD8 + T细胞浸润和程序性细胞死亡配体1表达相关。此外,具有CD8 + T细胞浸润和轻度CD33 +髓样细胞浸润的MCC与改善的结局(无复发和总体生存)显着且独立相关。
局限性
抽样偏差和回顾性设计是潜在的研究局限性。
结论
CD33 +髓样细胞和CD8 + T淋巴细胞的浸润定义了与预后改善相关的MCC子集。