Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-3-8
pubmed:abstractText
Transforming growth factor (TGF)-beta is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells may lead to tumor evasion from the host immune surveillance and tumor progression. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. The mouse TRAMP-C2 prostate cancer cells produced large amounts of TGF-beta1 and were used as an experimental model. C57BL/6 mice were primed with irradiated TRAMP-C2 cells. CD8+ T cells were isolated from the spleen of primed animals, were expanded ex vivo, and were rendered TGF-beta insensitive by infecting with a retrovirus containing dominant-negative TGF-beta type II receptor. Results of in vitro cytotoxic assay revealed that these CD8+ T cells showed a specific and robust tumor-killing activity against TRAMP-C2 cells but were ineffective against an irrelevant tumor line, B16-F10. To determine the in vivo antitumor activity, recipient mice were challenged with a single injection of TRAMP-C2 cells for a period up to 21 days before adoptive transfer of CD8+ T cells was done. Pulmonary metastasis was either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. Results of immunofluorescent studies showed that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis in tumor cells. Furthermore, transferred tumor-reactive TGF-beta-insensitive CD8+ T cells were able to persist in tumor-bearing hosts but declined in tumor-free animals. These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for cancer therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1761-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15753372-Adoptive Transfer, pubmed-meshheading:15753372-Animals, pubmed-meshheading:15753372-Apoptosis, pubmed-meshheading:15753372-CD8-Positive T-Lymphocytes, pubmed-meshheading:15753372-Fluorescent Antibody Technique, pubmed-meshheading:15753372-Genes, Dominant, pubmed-meshheading:15753372-Green Fluorescent Proteins, pubmed-meshheading:15753372-Lung Neoplasms, pubmed-meshheading:15753372-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:15753372-Male, pubmed-meshheading:15753372-Melanoma, Experimental, pubmed-meshheading:15753372-Mice, pubmed-meshheading:15753372-Mice, Inbred C57BL, pubmed-meshheading:15753372-Plasminogen Activator Inhibitor 1, pubmed-meshheading:15753372-Prostatic Neoplasms, pubmed-meshheading:15753372-Protein-Serine-Threonine Kinases, pubmed-meshheading:15753372-Receptors, Transforming Growth Factor beta, pubmed-meshheading:15753372-Retroviridae, pubmed-meshheading:15753372-Skin Neoplasms, pubmed-meshheading:15753372-Spleen, pubmed-meshheading:15753372-T-Lymphocytes, Cytotoxic, pubmed-meshheading:15753372-Transfection, pubmed-meshheading:15753372-Transforming Growth Factor beta
pubmed:year
2005
pubmed:articleTitle
Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer.
pubmed:affiliation
Department of Urology, Northwestern University's Feinberg School of Medicine, Chicago, Illinois 60611, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.