Loss of Tumorigenicity and Increased Immunogenicity Induced by Interleukin-10 Gene Transfer in B16 Melanoma Cells
作者:
Catherine M. Grard,
Catherine Bruyns,
Anne Delvaux,
Nathalie Baudson,
Jean-Louis Dargent,
Michel Goldman,
Thierry Velu,
期刊:
Human Gene Therapy
(MAL Available online 1996)
卷期:
Volume 7,
issue 1
页码: 23-31
ISSN:1043-0342
年代: 1996
DOI:10.1089/hum.1996.7.1-23
出版商: Mary Ann Liebert, Inc.
数据来源: MAL
摘要:
ABSTRACTBecause interleukin-10 (IL-10) has potent immunosuppressive and anti-inflammatory properties and is produced by some cancers, we hypothesized that its production might play a role in carcinogenesis by inhibiting adequate antitumoral immune responses. To test this hypothesis, retroviral vectors containing the IL-10 cDNA were generated and used to infect B16F1 melanoma cells that were injected subcutaneously in syngeneic mice. Surprisingly, IL-10 gene transfer resulted in a loss of tumorigenicity that was proportional to the amount of IL-10 secreted. Histological analysis showed massive area of necrosis of these tumor cells, with infiltration of polymorphic inflammatory cells. Parental cells simultaneously implanted had decreased tumorigenicity only when mixed with IL10-producing cells, but not when injected contralaterally, suggesting that their eradication is mediated mostly by a local phenomenon. Host T lymphocytes and natural killer (NK) cells were involved in this eradication because IL-10-producing cells grew in nude mice and in CD8or NK-depleted mice. Finally, mice injected with IL-10-secreting cells developed an antitumoral systemic immune response able to protect them against a subsequent challenge with parental cells. These results demonstrate that, in some settings, IL10 may havein vivoimmunostimulating and proinflammatory properties that need to be considered in its therapeutic development.
点击下载:
PDF
(9249KB)
返 回