Linked Life Data

16785502

Source:http://linkedlifedata.com/resource/pubmed/id/16785502

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-6-20
pubmed:abstractText
Studies in cancer patients have suggested that breast tumors recruit regulatory T cells (Tregs) into the tumor microenvironment. The extent to which local Tregs suppress antitumor immunity in breast cancer is unknown. We questioned whether inhibiting systemic Tregs with an IL-2 immunotoxin in a model of neu-mediated breast cancer, the neu-transgenic mouse, could impact disease progression and survival. As in human breast cancer, cancers that develop in these mice attract Tregs into the tumor microenvironment to levels of approximately 10-25% of the total CD4+ T cells. To examine the role of Tregs in blocking immune-mediated rejection of tumor, we depleted CD4+CD25+ T cells with an IL-2 immunotoxin. The treatment depleted Tregs without concomitant lymphopenia and markedly inhibited tumor growth. Depletion of Tregs resulted in a persistent antitumor response that was maintained over a month after the last treatment. The clinical response was immune-mediated because adoptive transfer of Tregs led to a complete abrogation of the therapeutic effects of immunotoxin treatment. Further, Treg down-modulation was accompanied by increased Ag-specific immunity against the neu protein, a self Ag. These results suggest that Tregs play a major role in preventing an effective endogenous immune response against breast cancer and that depletion of Tregs, without any additional immunotherapy, may mediate a significant antitumor response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
84-91
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16785502-Animals, pubmed-meshheading:16785502-Cell Line, Tumor, pubmed-meshheading:16785502-Female, pubmed-meshheading:16785502-Forkhead Transcription Factors, pubmed-meshheading:16785502-Genes, erbB-2, pubmed-meshheading:16785502-Graft Rejection, pubmed-meshheading:16785502-Immune Tolerance, pubmed-meshheading:16785502-Immunotoxins, pubmed-meshheading:16785502-Interleukin-2, pubmed-meshheading:16785502-Lymphocyte Depletion, pubmed-meshheading:16785502-Lymphopenia, pubmed-meshheading:16785502-Mammary Neoplasms, Experimental, pubmed-meshheading:16785502-Mice, pubmed-meshheading:16785502-Mice, Inbred BALB C, pubmed-meshheading:16785502-Mice, Transgenic, pubmed-meshheading:16785502-Receptors, Interleukin-2, pubmed-meshheading:16785502-Recombinant Fusion Proteins, pubmed-meshheading:16785502-Ribonuclease, Pancreatic, pubmed-meshheading:16785502-T-Lymphocytes, Regulatory, pubmed-meshheading:16785502-Tumor Markers, Biological
pubmed:year
2006
pubmed:articleTitle
IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic mice.
pubmed:affiliation
Department of Immunology, Mayo Clinic College of Medicine, 342C Guggenheim, 200 First Street SW, Rochester, MN 55905, USA. knutson.keith@mayo.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural