Background: Cancer is both a systemic and a genetic disease. The pathogenesis of cancer might be related to\r\ndampened immunity. Host immunity recognizes nascent malignant cells ââ?¬â?? a process referred to as immune\r\nsurveillance. Augmenting immune surveillance and suppressing immune escape are crucial in tumor\r\nimmunotherapy.\r\nMethods: A recombinant plasmid capable of co-expressing granulocyte-macrophage colony- stimulating factor\r\n(GM-SCF), interleukin-21 (IL-21), and retinoic acid early transcription factor-1 (Rae-1) was constructed, and its effects\r\ndetermined in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for IL-2 and INF-? by\r\nELISA. Liver cancer specimens were isolated for Rae-1 expression by RT-PCR and Western blot, and splenocytes were\r\nanalyzed by flow cytometry.\r\nResults: The recombinant plasmid inhibited the growth of liver cancer and prolonged survival of tumor-loaded\r\nmice. Activation of host immunity might have contributed to this effect by promoting increased numbers and\r\ncytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following expression of GM-SCF, IL-21, and\r\nRae-1. By contrast, the frequency of regulatory T cells was decreased, Consequently, activated CTL and NK cells\r\nenhanced their secretion of INF-?, which promoted cytotoxicity of NK cells and CTL. Moreover, active CTL showed\r\ndramatic secretion of IL-2, which stimulates CTL. The recombinant expression plasmid also augmented Rae-1\r\nexpression by liver cancer cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer.\r\nConclusions: The recombinant expression plasmid inhibited liver cancer by a mechanism that involved activation\r\nof cell-mediated immunity and Rae-1 in liver cancer.
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