The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Science, National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.
Int J Mol Sci. 2022 Apr 25;23(9):4717. doi: 10.3390/ijms23094717.
Multiple Myeloma (MM) is a devastating malignancy that evades immune destruction using multiple mechanisms. The NKp44 receptor interacts with PCNA (Proliferating Cell Nuclear Antigen) and may inhibit NK cells' functions. Here we studied in vitro the expression and function of PCNA on MM cells. First, we show that PCNA is present on the cell membrane of five out of six MM cell lines, using novel anti-PCNA mAb developed to recognize membrane-associated PCNA. Next, we stained primary bone marrow (BM) mononuclear cells from MM patients and showed significant staining of membrane-associated PCNA in the fraction of CD38CD138 BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN-γ-secretion and degranulation. Our results highlight the possible blocking of the NKp44-PCNA immune checkpoint by the mAb 14-25-9 antibody to enhance NK cell responses against MM, providing a novel treatment option.
多发性骨髓瘤（MM）是一种恶性肿瘤，它通过多种机制逃避免疫破坏。NKp44 受体与 PCNA（增殖细胞核抗原）相互作用，可能抑制 NK 细胞的功能。在这里，我们研究了 MM 细胞上 PCNA 的表达和功能。首先，我们使用新开发的识别膜结合 PCNA 的抗 PCNA mAb 显示，六种 MM 细胞系中的五种细胞系的细胞膜上存在 PCNA。接下来，我们对 MM 患者的骨髓（BM）单核细胞进行染色，并显示在包含 MM 细胞的 CD38CD138 BM 细胞的膜结合 PCNA 分数中存在明显染色。重要的是，阻断 MM 细胞上的膜 PCNA 增强了 NK 细胞的活性，包括 IFN-γ 分泌和脱颗粒。我们的研究结果强调了通过 mAb 14-25-9 抗体阻断 NKp44-PCNA 免疫检查点以增强 NK 细胞对 MM 的反应的可能性，为治疗提供了新的选择。
