Radiation Oncology Department, University Hospital Morvan, 2 avenue Foch, 29200, Brest, France.
Department of Dermatology, University Hospital Morvan, Brest, France.
J Cancer Res Clin Oncol. 2021 Sep;147(9):2569-2578. doi: 10.1007/s00432-021-03676-6. Epub 2021 Jun 11.
The aim of this study was to evaluate prognostic factors in patients with non-metastatic Merkel cell carcinoma (MCC), with a particular focus on immunological markers such as TILs subtyping (CD3, CD8, CD68, FoxP3, PD-L1 and PD-1) and MCPyV.
Patients treated for a non-metastatic MCC with oncologic surgical resection followed or not by adjuvant radiotherapy between 01/2007 and 12/2018 were analyzed. Local and regional control (LC, RC), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated. Clinical variables analyzed included age, gender, performance status, comorbidity, tumor size, location and presentation type, extension, oncologic resection and adjuvant radiotherapy. Pathological variables analyzed included type of tumor-infiltrating lymphocytes, CD3, CD8, CD68, PD-L1 expression on immune cells and tumors cells, PD-1, FoxP3 and MCPyV, assessed with immunohistochemistry (IHC).
77 patients were included. After a median follow-up of 18 months (range 0.2-144), the 1-year LC, RC, DMFS and OS were 83%, 60%, 82% and 75%, respectively. In multivariate analysis, a percentage of PD-L1 expression by immune cells ≥ 1% was significantly correlated with improvement of RC (p = 0.012), DMFS (p = 0.003) and OS (p = 0.006). Adjuvant radiotherapy significantly improved DMFS (p = 0.021) and OS (0.041) rates. There was a correlation between the presence of MCPyV + and the expression of PD-L1 on IC (p = 0.05) and TC (p = 0.03).
PD-L1 expression by immune and tumor cells in non-metastatic MCC seems to significantly improve outcome in patients who did not received PD-1/PD-L1 inhibitors. Prospective studies are needed to confirm our hypothesis.
本研究旨在评估非转移性 Merkel 细胞癌（MCC）患者的预后因素，特别关注免疫标志物，如 TIL 分型（CD3、CD8、CD68、FoxP3、PD-L1 和 PD-1）和 MCPyV。
分析了 2007 年 1 月至 2018 年 12 月期间接受非转移性 MCC 肿瘤切除术，且术后行或未行辅助放疗的患者。评估局部和区域控制（LC、RC）、无远处转移生存（DMFS）和总生存（OS）。分析的临床变量包括年龄、性别、表现状态、合并症、肿瘤大小、位置和表现类型、肿瘤扩展、肿瘤切除术和辅助放疗。分析的病理变量包括肿瘤浸润淋巴细胞、CD3、CD8、CD68、免疫细胞和肿瘤细胞 PD-L1 表达、PD-1、FoxP3 和 MCPyV 的类型，通过免疫组化（IHC）进行评估。
共纳入 77 例患者。中位随访 18 个月（范围 0.2-144）后，1 年 LC、RC、DMFS 和 OS 分别为 83%、60%、82%和 75%。多变量分析显示，免疫细胞 PD-L1 表达百分比≥1%与 RC（p=0.012）、DMFS（p=0.003）和 OS（p=0.006）改善显著相关。辅助放疗显著改善了 DMFS（p=0.021）和 OS（p=0.041）率。MCPyV+与 IC（p=0.05）和 TC（p=0.03）上 PD-L1 表达之间存在相关性。
非转移性 MCC 中免疫和肿瘤细胞 PD-L1 表达似乎显著改善了未接受 PD-1/PD-L1 抑制剂治疗的患者的预后。需要前瞻性研究来证实我们的假设。
