真菌样白斑病(MF)和塞扎里综合征(SS)是原发性皮肤T细胞淋巴瘤(CTCL)中最常见的类型。增殖细胞核抗原(PCNA)在癌细胞的细胞表面上表达(csPCNA)，而在正常细胞上没有表达。它通过与自然杀伤(NK)细胞相互作用，通过与NK抑制性受体NKp44结合，起到免疫检查点配体的作用，从而抑制NK的细胞毒性。建立了一种单克隆抗体(mAb14)来检测癌细胞上的csPCNA，并阻断其与NKp44的相互作用。本研究使用免疫染色、成像流式细胞术、流式细胞术、细胞分选、细胞周期分析、酶联免疫吸附试验和NK细胞细胞毒试验，分析了三种CTCL细胞系和来自SS患者和健康供体的外周血单个核细胞(PBMCs)中的csPCNA，与核PCNA(nPCNA)的单克隆抗体PC10进行比较。mAb14成功地检测到与G2/M期相关的存活CTCL细胞系膜上和细胞质中的PCNA。在塞扎里综合征的PBMCs中，csPCNA表达在具有非典型形态的淋巴瘤细胞上，而在正常细胞上没有表达。此外，在来自健康供体的PBMCs上也没有表达。在外周血中NK细胞(pNK)与CTCL细胞系共培养中，mAb14增加了IFN-γ的分泌，表明pNK活性的重新激活。然而，mAb14没有增强pNK细胞对CTCL细胞系的细胞毒活性。mAb14检测到的csPCNA的独特表达提示，csPCNA和mAb14可能分别作为SS和可能的其他CTCL变异的潜在生物标志物和工具。

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants.