| pubmed-article:21708958 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C0087111 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1516031 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1415846 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1424734 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C2698651 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1556066 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1619636 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C0127400 | lld:lifeskim |
| pubmed-article:21708958 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:21708958 | pubmed:issue | 16 | lld:pubmed |
| pubmed-article:21708958 | pubmed:dateCreated | 2011-8-15 | lld:pubmed |
| pubmed-article:21708958 | pubmed:abstractText | The anti-CTL-associated antigen 4 (anti-CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti-CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells expressing the inducible costimulator (ICOS) molecule, a T-cell-specific molecule that belongs to the CD28/CTLA-4/B7 immunoglobulin superfamily. ICOS and its ligand (ICOSL) have been shown to play diverse roles in T-cell responses such as mediating autoimmunity as well as enhancing the development/activity of regulatory T cells. These seemingly opposing roles have made it difficult to determine whether the ICOS/ICOSL pathway is necessary for antitumor responses. To determine whether the ICOS/ICOSL pathway might play a causal role in the antitumor effects mediated by anti-CTLA-4, we conducted studies in ICOS-sufficient and ICOS-deficient mice bearing B16/BL6 melanoma. We show that ICOS(+) T cells comprised a population of Th1 cytokine producing and tumor antigen-specific effector cells. Furthermore, in the absence of ICOS, antitumor T-cell responses elicited by anti-CTLA-4 are significantly diminished, thereby impairing tumor rejection. Our findings establish that the ICOS/ICOSL pathway is necessary for the optimal therapeutic effect of anti-CTLA-4, thus implicating this pathway as a target for future combinatorial strategies to improve the efficacy of anti-CTLA-4 therapy. | lld:pubmed |
| pubmed-article:21708958 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21708958 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21708958 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21708958 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:21708958 | pubmed:issn | 1538-7445 | lld:pubmed |
| pubmed-article:21708958 | pubmed:author | pubmed-author:FuTihuiT | lld:pubmed |
| pubmed-article:21708958 | pubmed:author | pubmed-author:SharmaPadmane... | lld:pubmed |
| pubmed-article:21708958 | pubmed:author | pubmed-author:HeQiumingQ | lld:pubmed |
| pubmed-article:21708958 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21708958 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:21708958 | pubmed:volume | 71 | lld:pubmed |
| pubmed-article:21708958 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21708958 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21708958 | pubmed:pagination | 5445-54 | lld:pubmed |
| pubmed-article:21708958 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:meshHeading | pubmed-meshheading:21708958... | lld:pubmed |
| pubmed-article:21708958 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21708958 | pubmed:articleTitle | The ICOS/ICOSL pathway is required for optimal antitumor responses mediated by anti-CTLA-4 therapy. | lld:pubmed |
| pubmed-article:21708958 | pubmed:affiliation | Departments of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. | lld:pubmed |
| pubmed-article:21708958 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21708958 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:21708958 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:50723 | entrezgene:pubmed | pubmed-article:21708958 | lld:entrezgene |
