Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses |
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Authors: | Byung-Gyu Kim Hong-Gu Joo In-Sung Chung Hee Yong Chung Hee-Jong Woo Yeon-Sook Yun |
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Institution: | (1) Laboratory of Immunology, Korea Cancer Center Hospital, KAERI, 215-4 Gongneung-dong, Nowon-ku, Seoul 139-706, Korea e-mail: ysyun@kcch.re.kr Tel.:+82-2-970-1307 Fax: +82-2-977-0381, KR;(2) Department of Microbiology and Immunology, College of Veterinary Medicine, Seoul National University, Suwon 441-704, Korea, KR |
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Abstract: | 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.
Received: 11 November 1999 / Accepted: 6 April 2000 |
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Keywords: | IL-10 Antisense oligodeoxynucleotide MHC B7-1 Tumor immunity |
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