Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
Leuk Lymphoma. 2012 Feb;53(2):305-14. doi: 10.3109/10428194.2011.615423. Epub 2011 Oct 24.
Malignant B-cells express measurable levels of human leukocyte antigen (HLA) class II proteins, but often escape immune recognition by CD4 + T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an up-regulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4 + T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through up-regulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma.
恶性 B 细胞表达可测量水平的人类白细胞抗原（HLA）Ⅱ类蛋白，但通常逃避 CD4+T 细胞的免疫识别。白藜芦醇（Resv）由于其潜在的化学预防和抗癌作用而成为众多研究的焦点，但从未在 B 细胞肿瘤免疫成分的调节中进行过测试。在这里，我们首次表明，Resv 通过改变肿瘤细胞中的免疫成分和 II 类呈递来增强 HLA Ⅱ类介导的 B 细胞淋巴瘤的免疫检测。Resv 处理诱导 B 淋巴瘤细胞中经典和非经典 HLA Ⅱ类蛋白（DR 和 DM）的上调。Resv 还改变了内溶酶体组织蛋白酶（Cat S、B 和 D）和一种硫醇还原酶（GILT），增加了 B 细胞淋巴瘤中 HLA Ⅱ类介导的抗原（Ag）加工及其随后被 CD4+T 细胞的识别。机制研究表明，Resv 通过上调 B 淋巴瘤细胞中 Rab 4B 蛋白的表达，激活了 Ag 呈递的再循环 II 类途径。这些发现表明，Resv 处理可以改善恶性 B 细胞的 HLA Ⅱ类介导的免疫识别，从而鼓励其在 B 细胞淋巴瘤的化疗免疫治疗中的潜在应用。
