Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-10-24
pubmed:abstractText
Anti-cancer immunotherapies aim to generate resolution of all existing tumors, including inaccessible ones, and provide long-term protection against recurrence. This is rarely achieved. Thus, we aimed to determine if the tumor microenvironment could be turned into a potent 'self'-vaccine site. Our target was to eradicate larger tumor burdens. Our models respond to single-agent immunotherapies; however, they fail at a precisely defined 'cut-off' tumor burden. Thus, this system was used to define the immune mechanisms required to mediate regression of larger tumors that are resistant to mono-immunotherapies. We report that direct injection of IL-2 with agonist anti-CD40 antibody into the tumor bed resulted in permanent resolution of treated and untreated distal tumors. Tumor-infiltrating CD8(+) T cells and neutrophils collaborated to eradicate treated tumors, IFNgamma was not critical and protective memory was preserved. This approach relied only on tumor antigens expressed within the tumor microenvironment. It also avoided systemic toxicities, did not require chemotherapy or surgery and is clinically useful because only one tumor site has to be accessible for treatment. We conclude that provoking intra-tumoral inflammation skews the tumor microenvironment from tumorigenic to immunogenic, resulting in the resolution of treated and untreated distal tumors, as well long-term protective memory.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1460-2377
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1467-79
pubmed:meshHeading
pubmed-meshheading:18824504-Animals, pubmed-meshheading:18824504-Antibodies, Monoclonal, pubmed-meshheading:18824504-Antigens, CD40, pubmed-meshheading:18824504-Asbestos, pubmed-meshheading:18824504-CD4-Positive T-Lymphocytes, pubmed-meshheading:18824504-CD8-Positive T-Lymphocytes, pubmed-meshheading:18824504-Cancer Vaccines, pubmed-meshheading:18824504-Cell Line, pubmed-meshheading:18824504-Humans, pubmed-meshheading:18824504-Immunologic Memory, pubmed-meshheading:18824504-Immunotherapy, pubmed-meshheading:18824504-Injections, Intravenous, pubmed-meshheading:18824504-Interleukin-2, pubmed-meshheading:18824504-Lymphocyte Depletion, pubmed-meshheading:18824504-Mesothelioma, pubmed-meshheading:18824504-Mice, pubmed-meshheading:18824504-Mice, Inbred BALB C, pubmed-meshheading:18824504-Mice, Inbred C57BL, pubmed-meshheading:18824504-Mice, Nude, pubmed-meshheading:18824504-Neoplasms, Experimental, pubmed-meshheading:18824504-Recombinant Proteins
pubmed:year
2008
pubmed:articleTitle
Deliberately provoking local inflammation drives tumors to become their own protective vaccine site.
pubmed:affiliation
School of Biomedical Sciences, Curtin University, Kent St Bentley, Perth, Western Australia 6102, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't