Melero I, Bach N, Hellström K E, Aruffo A, Mittler R S, Chen L
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, USA.
Eur J Immunol. 1998 Mar;28(3):1116-21. doi: 10.1002/(SICI)1521-4141(199803)28:03<1116::AID-IMMU1116>3.0.CO;2-A.
We have explored the role of an activation-induced T cell molecule, 4-1BB (CDw137), in the amplification of tumor immunity by retrovirus-mediated transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte (CTL) response and long-term immunity against wild-type tumor. The optimal effect of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this interaction by antibodies down-regulated the expression of 4-1BB on T cells and decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single transfectants were effective, suggesting a synergistic effect between the 4-1BB and the CD28 co-stimulatory pathways. Our results underscore the importance of the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune response.
我们通过逆转录病毒介导将4-1BB配体（4-1BBL）转导至肿瘤细胞中，探讨了活化诱导的T细胞分子4-1BB（CDw137）在增强肿瘤免疫中的作用。接种表达4-1BBL的P815肿瘤细胞的小鼠产生了强烈的细胞毒性T淋巴细胞（CTL）反应，并对野生型肿瘤产生了长期免疫力。4-1BBL在刺激CTL方面的最佳效果需要B7-CD28相互作用，因为抗体阻断这种相互作用会下调T细胞上4-1BB的表达并降低CTL活性。此外，在免疫原性较差的AG104A肉瘤中共表达4-1BBL和B7-1可增强效应CTL的诱导及野生型肿瘤的排斥，而单独转染4-1BBL或B7-1均无效，这表明4-1BB和CD28共刺激途径之间存在协同效应。我们的结果强调了4-1BB T细胞刺激途径在增强抗肿瘤免疫反应中的重要性。
