Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-7-3
pubmed:abstractText
Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8(+) T cells, vascular injury, disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on CD8(+) T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-gamma-dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-gamma production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of tumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-gamma and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8(+) T cell-mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-10229107, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-10395644, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-10605016, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-10815886, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-11145697, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-11238618, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-1358972, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-1372394, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-1578139, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-1672545, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-2160521, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-2418110, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-6367046, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-6427925, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-6854757, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7502042, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7511063, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7515183, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7518614, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7521890, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7528775, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7532682, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7538593, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7566174, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7636204, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7693996, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7706720, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7906963, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7913943, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-7994020, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8104230, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8564954, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8611715, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8615973, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8640772, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8841000, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8847724, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8910274, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-8946836, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9012700, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9020068, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9064324, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9137109, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9300678, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9697833, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9755337, http://linkedlifedata.com/resource/pubmed/commentcorrection/11435457-9755338
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-62
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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