Inhibition of interleukin-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 diverse cell types of the immune system. It inhibits the antigen-presenting capacity of monocytes/macrophages and stimulates T cell proliferation. Although many tumors spontaneously release IL-10, the physiological relevance of this phenomenon to the in vivo antitumor immune response is not known. To elucidate the physiological role of tumor-released IL-10, we used IL-10-specific antisense oligodeoxynucleotides (AS-ODN) for the inhibition of IL-10 production 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 enhancement of the expression of major histocompatibility complex (MHC) class 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 Balb/c mice. The mice implanted with MOPC-IL10AS effectively rejected the tumor graft, and showed strong cytotoxic T lymphocyte (CTL) activity against the parental MOPC 315 cells. In addition, MOPC-IL10AS were more effective as stimulator cells in mixed lymphocyte/ tumor cell culture, and as target cells in a CTL assay. These results imply that IL-10 spontaneously released from MOPC 315 cells inhibits their immunogenicity and that the inhibition of IL-10 production by IL-10 AS-ODN may be a way to enhance the host cellular antitumor immune response.
Kim
B G
BG
Laboratory of Immunology, Korea Cancer Center Hospital, KAERI, Seoul.
Joo
H G
HG
Chung
I S
IS
Chung
H Y
HY
Woo
H J
HJ
Yun
Y S
YS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D016376:Oligonucleotides, Antisense; D016753:Interleukin-10; D013936:Thymidine