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用碳酸酐酶 IX 和鲍曼不动杆菌外膜蛋白 A 脉冲处理的树突状细胞对肾细胞癌的免疫刺激活性。

Immunostimulatory activity of dendritic cells pulsed with carbonic anhydrase IX and Acinetobacter baumannii outer membrane protein A for renal cell carcinoma.

机构信息

Department of Physiology, Kyungpook National University School of Medicine, Daegu, 700-422, Republic of Korea.

出版信息

J Microbiol. 2011 Feb;49(1):115-20. doi: 10.1007/s12275-011-1037-x. Epub 2011 Mar 3.

Abstract

Dendritic cell (DC)-based immunotherapy is a potent therapeutic modality for treating renal cell carcinoma (RCC), but development of antigens specific for tumor-targeting and anti-tumor immunity is of great interest for clinical trials. The present study investigated the ability of DCs pulsed with a combination of carbonic anhydrase IX (CA9) as an RCC-specific biomarker and Acinetobacter baumannii outer membrane protein A (AbOmpA) as an immunoadjuvant to induce anti-tumor immunity against murine renal cell carcinoma (RENCA) in a murine model. Murine bone-marrow-derived DCs pulsed with a combination of RENCA lysates and AbOmpA were tested for their capacity to induce DC maturation and T cell responses in vitro. A combination of RENCA lysates and AbOmpA up-regulated the surface expression of co-stimulatory molecules, CD80 and CD86, and the antigen presenting molecules, major histocompatibility (MHC) class I and class II, in DCs. A combination of RENCA lysates and AbOmpA also induced interleukin-12 (IL-12) production in DCs. Next, the immunostimulatory activity of DCs pulsed with a combination of CA9 and AbOmpA was determined. A combination of CA9 and AbOmpA up-regulated the surface expression of co-stimulatory molecules and antigen presenting molecules in DCs. DCs pulsed with a combination of CA9 and AbOmpA effectively secreted IL-12 but not IL-10. These cells interacted with T cells and formed clusters. DCs pulsed with CA9 and AbOmpA elicited the secretion of interferon-γ and IL-2 in T cells. In conclusion, a combination of CA9 and AbOmpA enhanced the immunostimulatory activity of DCs, which may effectively induce anti-tumor immunity against human RCC.

摘要

树突状细胞(DC)为基础的免疫疗法是治疗肾细胞癌(RCC)的有效治疗方法,但开发针对肿瘤靶向和抗肿瘤免疫的抗原对于临床试验非常有意义。本研究探讨了用碳酸酐酶 IX(CA9)作为 RCC 特异性生物标志物和鲍曼不动杆菌外膜蛋白 A(AbOmpA)作为免疫佐剂的组合脉冲 DC 诱导针对小鼠肾细胞癌(RENCA)的抗肿瘤免疫的能力。用 RENCA 裂解物和 AbOmpA 的组合脉冲的小鼠骨髓来源的 DC 用于体外检测诱导 DC 成熟和 T 细胞反应的能力。RENCA 裂解物和 AbOmpA 的组合上调了共刺激分子 CD80 和 CD86 的表面表达以及 DC 中的主要组织相容性(MHC)I 类和 II 类抗原呈递分子。RENCA 裂解物和 AbOmpA 的组合还诱导了 DC 中白细胞介素-12(IL-12)的产生。接下来,确定了用 CA9 和 AbOmpA 的组合脉冲的 DC 的免疫刺激活性。CA9 和 AbOmpA 的组合上调了共刺激分子和抗原呈递分子在 DC 中的表面表达。用 CA9 和 AbOmpA 的组合脉冲的 DC 有效地分泌了 IL-12,但没有分泌 IL-10。这些细胞与 T 细胞相互作用并形成簇。用 CA9 和 AbOmpA 脉冲的 DC 可刺激 T 细胞分泌干扰素-γ和 IL-2。总之,CA9 和 AbOmpA 的组合增强了 DC 的免疫刺激活性,这可能有效地诱导针对人 RCC 的抗肿瘤免疫。

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