下调ROR1表达削弱黑色素瘤疫苗抗瘤效应  

The vaccine made from melanoma cells with down-regulated expression of ROR1 lead to weakened antitumor activity

作　　者：王玲 梅峰 薛蕊 李淼[1] 徐慧 赵枫姝[1] 窦骏[1] WANG Ling;MEI Feng;XUE Rui;LI Miao;XU Hui;ZHAO Feng-shu;DOU Jun(Department of Pathogenic Biology and Immunology,Southeast University School of Medicine,Nanjing210009,China)

机构地区：[1]东南大学医学院病原生物学与免疫学系,南京210009

出　　处：《现代免疫学》2021年第6期455-461,共7页Current Immunology

基　　金：国家自然科学基金面上项目(81572887)。

摘　　要：黑色素瘤细胞高表达受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase like orphan receptor 1, ROR1),其可促进肿瘤细胞的增殖、侵袭和转移,是治疗黑色素瘤的重要靶标。为探讨下调黑色素瘤细胞ROR1表达对制备的黑色素瘤疫苗抗瘤效应的影响,通过慢病毒载体shRNA下调B16F10细胞ROR1分子表达。反复冻融各实验组B16F10细胞制备疫苗,免疫C57BL/6小鼠3次后,用B16F10细胞攻击小鼠,以评价免疫鼠的免疫系统活性和抗肿瘤效应。结果显示,与对照组相比,shROR1/B16F10细胞ROR1分子表达水平显著降低(P<0.01),用其制备疫苗免疫小鼠会抑制免疫系统对肿瘤细胞的攻击及机体抗瘤效应。由此,ROR1是黑色素瘤疫苗的重要靶点,下调ROR1表达将导致黑色素瘤疫苗免疫活性减弱而影响免疫鼠抗黑色素瘤效应。Receptor tyrosine kinase like orphan receptor 1(ROR1), which is highly expressed in melanoma cells, can promote tumor cell proliferation, invasion, and metastasis, and is an important target of melanoma therapy. To investigate the influence of reduced expression of ROR1 in melanoma cells on its ability to stimulate the anti-tumor immune response, we used lentiviral vector-mediated shRNA to down-regulate the expression of ROR1 in B16 F10 cells. Then all B16 F10 cells were undergone multiple freeze-thaw and those cells were used to immunize C57 BL/6 mice for three times. Mice were challenged with tumor cells after the last vaccination, and the effect of immunocompetence and anti-melanoma activity were further evaluated. Compared with the control group, the expression of ROR1 in shROR1/B16 F10 cells was significantly reduced(P<0.01), the efficiency of antagonizing the immune system attack on tumor cells was decreased and the anti-tumor effect was significantly weakened in the wake of reduced immune responses. Therefore, ROR1 is an important target of the melanoma vaccine. Down-regulated ROR1 expression resulted in reduced immune activities of B16 F10 cell vaccine and its anti-melanoma effect.

关 键 词：黑色素瘤 受体酪氨酸激酶样孤儿受体1 肿瘤疫苗 免疫效应 

分 类 号：R392.12[医药卫生—免疫学]