Background: Merkel cell carcinoma (MCC) is a rare and frequently fatal form of skin cancer. Apart from Programmed Cell Death Protein 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) signaling, there is a lack of knowledge regarding other immune checkpoint molecules. Recent studies have observed elevated glycoprotein CD200 (also known as OX-2) mRNA expression in in different types of tumors, with CD200R-expressing myeloid cells present in the tumor microenvironment. However, the potential role of the CD200/CD200 axis as an additional checkpoint modulator remains widely unexplored. The aim of this study was to determine the intratumoral protein expression of CD200 as well as CD200R in a larger cohort of MCC patients and to correlate the expression levels with patients’ outcomes. Methods: In this multicenter study, we investigated 68 patients with MCC (68 primary tumors and 15 corresponding metastases). Immunohistochemistry (IHC) was performed for CD200 as well as CD200R. Digital quantification and analysis of IHC were performed using QuPath-0.2.3. Results: CD200 and CD200R expression was observed in 100% of cases. Univariate analysis revealed that low CD200 expression in primary tumors (p= 0.0007, HR 9.35), male sex (p= 0.045, HR 2.41), and immunosuppression (p= 0.0031, HR 6.36) were significantly associated with MCC relapse. Low CD200 expression was also linked to prior immune checkpoint inhibitors (ICI) and/or chemotherapy treatment (p= 0.037). Multivariable analysis confirmed that low CD200 expression (p= 0.0012, HR 5.25) and immunosuppression (p= 0.0056, HR 4.11) were independent predictors of MCC relapse. Conclusions: Expression of CD200/CD200R proteins is very high in MCC and may thus be of diagnostic value. More importantly, low intratumoral CD200 protein expression in primary MCC represents a robust independent predictor of MCC relapse.
背景：默克尔细胞癌（MCC）是一种罕见且常致命的皮肤癌。除程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）信号通路外，目前对其他免疫检查点分子的认知仍较为有限。近期研究发现，多种肿瘤类型中糖蛋白CD200（亦称OX-2）的mRNA表达水平升高，且肿瘤微环境中存在表达CD200R的髓系细胞。然而，CD200/CD200R轴作为潜在免疫检查点调节剂的作用机制尚未得到充分探索。本研究旨在通过较大规模MCC患者队列，检测肿瘤内CD200及CD200R蛋白表达水平，并分析其与患者预后的相关性。方法：这项多中心研究纳入68例MCC患者（68个原发灶及15个对应转移灶）。采用免疫组织化学（IHC）检测CD200与CD200R表达，使用QuPath-0.2.3软件进行数字化定量分析。结果：所有病例均检测到CD200与CD200R表达。单变量分析显示：原发灶低CD200表达（p=0.0007，HR 9.35）、男性（p=0.045，HR 2.41）及免疫抑制状态（p=0.0031，HR 6.36）与MCC复发显著相关。低CD200表达还与既往接受免疫检查点抑制剂（ICI）和/或化疗治疗相关（p=0.037）。多变量分析证实，低CD200表达（p=0.0012，HR 5.25）和免疫抑制状态（p=0.0056，HR 4.11）是MCC复发的独立预测因子。结论：CD200/CD200R蛋白在MCC中呈高表达，可能具有诊断价值。更重要的是，MCC原发灶肿瘤内低CD200蛋白表达是预测疾病复发的强效独立指标。
肿瘤(癌症)患者之家