Interleukin-23 (IL-23), a novel cytokine composed of a newly identified p19 molecule and the p40 subunit of IL-12, can stimulate the proliferation in vitro of memory T cells. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p19-linked p40 gene (Colon 26/IL-23) could produce antitumor effects in inoculated mice. The growth of Colon 26/IL-23 tumors developed in immunocompetent mice was significantly retarded and the tumors disappeared thereafter. Spleen cells from the mice that received Colon 26/IL-23 cells produced significant amounts of interferon-γ, when they were cultured with irradiated Colon 26 but not irrelevant cells. Depletion of CD8+T cells suppressed the production of interferon-γ. The mice that had rejected Colon 26/IL-23 tumors were resistant to subsequent challenge of parent but not irrelevant tumor cells. Colon 26/IL-23 tumors were not rejected in nude mice but the growth was retarded compared to parent tumors. Treatment of nude mice with anti-asialo GM1 antibody did not influence the growth of Colon 26/IL-23 tumors. These data suggest that expression of IL-23 in tumors produces T cell-dependent antitumor effects and induces systemic immunity.

DNA polymerase κ (POLκ) is a low fidelity translesional DNA polymerase implicated in spontaneous and DNA damage-induced mutagenesis. We have previously shown that POLκ was frequently overexpressed in human lung cancer tissues as compared with their matched nontumorous tissue counterpart. In the present study, we found a close correlation between elevated POLκ expression and p53 inactivation in lung cancer tissues. To investigate whether POLK expression might be regulated by p53, we have determined the transcriptional initiation site of POLK gene and examined its promoter activity in A549, H358-129, and PC-3 human lung cancer cell lines. Wild-type p53, but not a mutant p53 (R273H) devoid of the DNA-binding activity, strongly inhibited POLK promoter activity in these cells. In addition, POLK promoter exhibited a significantly higher activity in p53-/- murine embryo fibroblasts (MEF) than in p53+√- and p53+√+ MEF. These results link p53 status with POLκ expression and suggest that loss of p53 function may in part contribute to the observed POLκ upregulation in human lung cancers.

Opioid receptor like 1 (ORL1) receptor is a novel member of the opioid receptor family, which was not bound by any of the typical opioid receptor ligands but bound by the recently discovered nociceptin (also termed orphanin FQ) with high af