Maciejewski Ryszard, Radej Sebastian, Furmaga Jacek, Chrościcki Andrzej, Rudzki Sławomir, Roliński Jacek, Wallner Grzegorz
Pol Przegl Chir. 2013 Dec;85(12):714-20. doi: 10.2478/pjs-2013-0109.
Dendritic cells are heterogeneous population of the leukocytes and most potent APC in activation of naive T lymphocytes. Therefore the DCs generated in vitro are under research for their application in anti-tumor immunotherapy. The aim of the study was generation of the immature dendritic cells from peripheral blood monocytes collected from colorectal cancer patients and comparison of their ability to endocytosis, cytokine production and immunophenotype to DCs generated from healthy donors.
16 adenocarcinoma stage II patients were included in the study. Dendritic cells were generated in the presence of rhGM-CSF and IL-4. PBMC were isolated from the blood of patients and 16 healthy donors - control group. Immunophenotype, ability of endocytosis of Dextran- FITC as well as intracellular IL-12 expression of the generated dendritic cells was measured using flow cytometry. The cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration in the supernatants of DCs culture was measured by ELISA.
The percentage of the immature dendritic cells and expression of CD206 and CD209 antigens was significantly higher in patients group (p <0.05 and p <0.001 respectively). Significantly (p <0.001) higher expression of the antigens which initiate the Th2 immune response (CD80-/CD86 + and B7-H2 + / CD209 +) was in the patients group. There were no differences in endocytosis ability and the cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration between investigated groups.
High immature markers expression on the generated dendritic cells together with identical endocytosis ability in patients group is advantageous in antitumor autologous cells immunotherapy planning. However there is one troubling fact--high expression of markers, which may induce tolerance to particular antigen. It seems to be more reasonable to use the autologous DCs in the antitumor immunotherapy, especially due to the incompatibility in allogenic cells in the context of HLA complex.
树突状细胞是白细胞的异质群体，是激活初始T淋巴细胞最有效的抗原呈递细胞（APC）。因此，体外产生的树突状细胞正在研究其在抗肿瘤免疫治疗中的应用。本研究的目的是从结直肠癌患者外周血单核细胞中生成未成熟树突状细胞，并比较其与健康供体产生的树突状细胞的内吞作用、细胞因子产生和免疫表型的能力。
16例II期腺癌患者纳入研究。在重组人粒细胞-巨噬细胞集落刺激因子（rhGM-CSF）和白细胞介素-4（IL-4）存在的情况下生成树突状细胞。从患者血液和16名健康供体（对照组）中分离外周血单个核细胞（PBMC）。使用流式细胞术测量生成的树突状细胞的免疫表型、异硫氰酸荧光素（FITC）标记葡聚糖的内吞能力以及细胞内白细胞介素-12（IL-12）的表达。通过酶联免疫吸附测定（ELISA）测量树突状细胞培养上清液中细胞因子（IL-6、IL-10、IL-12p70、干扰素-γ（IFN-γ））的浓度。
患者组未成熟树突状细胞的百分比以及CD206和CD209抗原的表达明显更高（分别为p<0.05和p<0.001）。患者组中启动Th2免疫反应的抗原（CD80-/CD86 +和B7-H2 + / CD209 +）的表达明显更高（p<0.001）。研究组之间的内吞能力和细胞因子（IL-6、IL-10、IL-12p70、IFN-γ）浓度没有差异。
患者组中生成的树突状细胞上高未成熟标志物表达以及相同的内吞能力在抗肿瘤自体细胞免疫治疗规划中是有利的。然而，有一个令人不安的事实——可能诱导对特定抗原耐受的标志物高表达。在抗肿瘤免疫治疗中使用自体树突状细胞似乎更合理，特别是由于在人类白细胞抗原（HLA）复合体背景下异体细胞的不相容性。
