Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1996-1-29
|
| pubmed:abstractText |
Unfractionated spleen cells taken from tumor-bearing mice 2 weeks after tumor implantation contained tumor-primed T cells which produced cytokines including IL-2 and IFN-gamma when cultured in vitro. With progressive tumor growth this initial lymphokine-producing capacity decreased. Here, we investigated the ability of IL-12 to (i) restore suppressed IFN-gamma production, (ii) cause tumor regression and (ii) induce anti-tumor protective immunity. Addition of rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearing mice resulted in a striking enhancement in the production of IFN-gamma compared with cultures of these cells in the absence of rIL-12 or of normal spleen cells in the presence of rIL-12. Five i.p. injections of rIL-12 into mice bearing s.c. tumors induced complete tumor regression. This was found when rIL-12 was given at early (1-2 weeks), intermediate (4-5 weeks) or even late (7 weeks) stages of tumor growth. Furthermore, IL-12-treated mice which rejected the primary tumor exhibited complete resistance to a rechallenge with the same tumor but did not reject a second syngenetic tumor. Immunohistochemical analyses following IL-12 treatment revealed that CD4+ and CD8+ T cells infiltrate the tumor. More importantly, IFN-gamma mRNA expression was observed in fresh tumor masses from tumor-bearing mice receiving IL-12 treatment. The importance of IFN-gamma was further demonstrated by the observation that the systemic administration of anti-IFN-gamma mAb prior to IL-12 treatment completely abrogated the anti-tumor effect of IL-12. Thus, these results indicate that administration of modest levels of rIL-12 to tumor-bearing mice results in tumor regression through mechanisms involving reversal of suppressed IFN-gamma production by anti-tumor T cells and the establishment of a tumor-specific protective immune response.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0953-8178
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
7
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1135-45
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8527411-Animals,
pubmed-meshheading:8527411-CD4-Positive T-Lymphocytes,
pubmed-meshheading:8527411-CD8-Positive T-Lymphocytes,
pubmed-meshheading:8527411-Fibrosarcoma,
pubmed-meshheading:8527411-Immune Tolerance,
pubmed-meshheading:8527411-Immunity, Innate,
pubmed-meshheading:8527411-Immunophenotyping,
pubmed-meshheading:8527411-Injections, Intraperitoneal,
pubmed-meshheading:8527411-Interferon-gamma,
pubmed-meshheading:8527411-Interleukin-12,
pubmed-meshheading:8527411-Lymphokines,
pubmed-meshheading:8527411-Male,
pubmed-meshheading:8527411-Mice,
pubmed-meshheading:8527411-Mice, Inbred BALB C,
pubmed-meshheading:8527411-Recombinant Proteins,
pubmed-meshheading:8527411-Remission Induction,
pubmed-meshheading:8527411-Spleen,
pubmed-meshheading:8527411-T-Lymphocytes,
pubmed-meshheading:8527411-Tumor Cells, Cultured
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-gamma production by anti-tumor T cells.
|
| pubmed:affiliation |
Biomedical Research Center, Osaka University Medical School, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|