Tatsumi K

Expression of Interleukin-22 in Murine Carcinoma Cells did not Influence Tumour Growth In Vivo but did Improve Survival of the Inoculated Hosts

Interleukin (IL)‐22, a novel cytokine belonging to the IL‐10 family, is secreted from activated T and natural killer cells and is possibly involved in inflammatory responses. We examined whether expression of the IL‐22 gene in murine colon carcinoma Colon 26 cells (Colon 26/IL‐22) could produce any antitumour effects in the inoculated mice. Although growth of Colon 26/IL‐22 tumours in syngeneic mice was not different from that of parent tumours, survival of the mice that were subcutaneously or intraperitoneally inoculated with Colon 26/IL‐22 tumours was significantly prolonged compared with the mice inoculated with parent tumours. Metastasis was not influenced by IL‐22 expressed in tumours. Expression of the IL‐22 receptor‐specific gene, IL‐22R, was not induced in spleen cells stimulated with concanavalin A, anti‐CD3 or anti‐CD40 antibody, despite constitutive expression of the IL‐10R2 gene, which encodes another component of the heterodimeric IL‐22 receptor complex. IL‐22 thereby does not directly act on immunocompetent cells, and IL‐22 expressed in tumours can favour apothanasia of inoculated hosts.

Administration of DNA Encoding the Interleukin-27 Gene Augments Antitumour Responses through Non-adaptive Immunity

DNA‐mediated immunization of a tumour antigen is a possible immunotherapy for cancer, and interleukin (IL)‐27 has diverse functions in adaptive immunity. In this study, we examined whether IL‐27 DNA administration enhanced antitumour effects in mice vaccinated with DNA encoding a putative tumour antigen, β‐galactosidase (β‐gal). An intramuscular injection of cardiotoxin before DNA administration facilitated the exogenous gene expression. In mice received β‐gal and IL‐27 DNA, growth of β‐gal‐positive P815 tumours was retarded and survival of the mice was prolonged. Development of β‐gal‐positive Colon 26 tumours was suppressed by vaccination of β‐gal DNA and further inhibited by additional IL‐27 DNA administration or IL‐12 family cytokines. Nevertheless, a population of β‐gal‐specific CD8+ T cells did not increase, and production of anti‐β‐gal antibody was not enhanced by IL‐27 DNA administration. Spleen cells from mice bearing IL‐27‐expressing Colon 26 tumours showed greater YAC‐1‐targeted cytotoxicity although CD3−/DX5+ natural killer (NK) cell numbers remained unchanged. Recombinant IL‐27 enhanced YAC‐1‐targeted cytotoxicity of IL‐2‐primed splenic NK cells and augmented a phosphorylation of signal transducer and activator of transcription 3 and an expression of perforin. These data collectively indicate that IL‐27 DNA administration activates NK cells and augments vaccination effects of DNA encoding a tumour antigen through non‐adaptive immune responses.