肿瘤细胞治疗研究
英文原题：Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma.
多发性骨髓瘤（MM）是一种破坏性恶性肿瘤，通过多种机制逃避免疫破坏。
多发性骨髓瘤（MM）是一种破坏性恶性肿瘤，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，并可能抑制NK细胞的功能。在此，我们在体外研究了PCNA在MM细胞上的表达和功能。首先，我们使用为识别膜相关PCNA而开发的新型抗PCNA mAb，显示PCNA存在于六个MM细胞系中的五个的细胞膜上。接下来，我们对MM患者的原代骨髓（BM）单核细胞进行了染色，并显示在含有MM细胞的CD38 + CD138 + BM细胞部分中，膜相关PCNA有显著染色。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- -分泌和脱颗粒。我们的结果突出了mAb 14-25-9抗体可能阻断NKp44-PCNA免疫检查点，以增强NK细胞对MM的应答，提供了一种新的治疗选择。
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 CD38 + CD138 + BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN- -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.
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