肿瘤细胞治疗研究
英文原题：Potassium/sodium cation carriers robustly upregulate CD20 antigen by targeting MYC, and synergize with anti- CD20 immunotherapies to eliminate malignant B cells.
我们的研究发现，纳摩尔浓度的盐霉素、莫能菌素、尼日利亚菌素和那拉霉素（一组钾/钠阳离子载体）能显著增强B细胞来源肿瘤细胞表面的CD20抗原表达，包括慢性淋巴细胞白血病和弥漫性大B细胞淋巴瘤的原代恶性细胞。
我们的研究揭示，纳摩尔浓度的盐霉素、莫能菌素、尼日利亚菌素和甲基盐霉素（一组钾/钠阳离子载体）可显著增强B细胞来源肿瘤细胞表面CD20抗原的表达，包括慢性淋巴细胞白血病和弥漫大B细胞淋巴瘤的原代恶性细胞。体外、离体和动物模型实验揭示了一种将盐霉素或莫能菌素与治疗性抗CD20单克隆抗体或抗CD20CAR-T 细胞联合使用的新方法，可显著改善非霍奇金淋巴瘤的治疗效果。RNA测序、基因编辑和化学抑制的结果将CD20上调的分子机制至少部分归因于MYC的下调，MYC是编码CD20的MS4A1基因的转录抑制因子。我们的发现提出阳离子载体作为靶向MYC癌基因的化合物，可与抗CD20抗体或过继性细胞疗法联合用于治疗非霍奇金淋巴瘤并减轻耐药性，而耐药性通常依赖于CD20抗原丢失，为改善患者预后提供了新的解决方案。
Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/ sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 chimeric antigen receptor T cells, significantly improving non-Hodgkin lymphoma therapy. The results of RNA sequencing, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20. Our findings propose the cation carriers as compounds targeting MYC oncogene, which can be combined with anti-CD20 antibodies or adoptive cellular therapies to treat non-Hodgkin lymphoma and mitigate resistance, which frequently depends on the CD20 antigen loss, offering new solutions to improve patient outcomes.
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