Inhibition of interieukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses

Interleukin-10 (IL-10) has both inhibitory and stimulatory effects on diver se cell types of the: immune system. It inhibits the antigen-presenting cap acity of monocytes/macrophages and stimulates T cell proliferation. Althoug h many tumors spontaneously release IL-10, the physiological relevance of t his phenomenon to the in vivo antitumor immune response is not known. To el ucidate the physiological role of tumor-released IL-10, we used IL-10-speci fic antisense oligodeoxynucleotides (AS-ODN) for the inhibition of IL-10 pr oduction from the tumor cells. Incubation of MOPC 315 plasmacytoma with IL- 10 AS-ODN in vitro resulted in inhibition of IL-10 production and also in e nhancement of the expression of major histocompatibility complex (MHC) clas s I, MHC class II, and B7-1 molecules. MOPC 315 cells incubated with IL-10 AS-ODN (MOPC-IL10AS) for 16 h in vitro showed reduced tumorigenicity in Bal b/c mice. The mice implanted with MOPC-IL10AS effectively rejected the tumo r graft, and showed strong cytotoxic T lymphocyte (CTL) activity against th e parental MOPC 315 cells. In addition, MOPC-IL10AS were more effective as stimulator cells in mixed lymphocyte/tumor cell culture, and as target cell s in a CTL assay. These results imply that IL-10 spontaneously released fro m MOPC 315 cells inhibits their immunogenicity and that the inhibition of I L-10 production by IL-IO AS-ODN may be a way to enhance the host cellular a ntitumor immune response.