4-1BB (CD137) Ligand Enhanced Anti-Tumor Immune Response against Mouse Forestomach Carcinoma In Vivo
4-1BB (CD137) Ligand Enhanced Anti-Tumor Immune Response against Mouse Forestomach Carcinoma In Vivo
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DOI：
10.1038/cmi.2008.47
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发表时间：
2008-10-01
影响因子：
24.1
通讯作者：
Shan, Baoen
中科院分区：
文献类型：
--
作者：
Li, Qiaoxia;Ai, Jun;Shan, Baoen
癌症的发生和发展与逃避免疫监视有关，低共刺激分子表达被认为是癌症逃避免疫系统的重要原因之一。4-1BB （CD137）是一种在活化T细胞表面表达的共刺激分子。4-1BB与其在抗原提呈细胞（APCs）上表达的天然配体（4-1BBL）的相互作用已被证明可增强t细胞介导的免疫。因此，我们检测了表达4-1BBL的小鼠癌细胞是否能在接种小鼠体内产生抗肿瘤作用。用4-1BBL基因转染小鼠前胃癌细胞（MFC/4-1BBL）。转导细胞在体外的增殖与亲本细胞无明显差异。然而，MFC/4-1BBL细胞发展成小肿瘤，并诱导更高的肿瘤浸润淋巴细胞（TIL）的细胞毒性。丝裂霉素C （MMC）处理的MFC/4-1BBL细胞免疫小鼠血清中细胞因子（ifn - γ、tnf - α和IL-2）的产生和脾细胞毒性T淋巴细胞（CTL）活性显著高于MMC处理的亲本MFC和MFC/pMKITneo细胞免疫小鼠。这些结果表明，4-1BBL基因修饰癌细胞可以产生抗肿瘤免疫应答。细胞与分子免疫学。2008;5(5):379-384。
Cancer occurrence and development has been demonstrated to be associated with escape from immune surveillance, and low costimulatory molecules expression has been considered as one of the important reasons for cancer evading the immune system. 4-1BB (CD137) is a costimulatory molecule expressed on the surface of activated T cells. Interaction of 4-1BB with its natural ligand (4-1BBL) expressed on antigen presenting cells (APCs) has been shown to amplify T-cell mediated immunity. We therefore examined whether murine cancer cells expressing 4-1BBL could produce antitumor effects in inoculated mice. Mouse forestomach carcinoma (MFC) cells were transfected with 4-1BBL gene (MFC/4-1BBL). The proliferation of the transduced cells in vitro was not different from that of parental cells. However, MFC/4-1BBL cells developed small tumors and induced higher cytotoxicity of tumor infiltration lymphocyte (TIL). Production of cytokines (IFN-gamma, TNF-alpha and IL-2) in serum and cytotoxic T lymphocyte (CTL) activity of splenocytes from mice immunized with mitomycin C (MMC)-treated MFC/4-1BBL cells were significantly higher than that from mice immunized with MMC-treated parental MFC and MFC/pMKITneo cells. These results suggest that modification of cancer cells with 4-1BBL gene can produce antitumor immune responses. Cellular & Molecular Immunology. 2008;5(5):379-384.