DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Junsik | ko |
dc.contributor.author | Kwon, Minsuk | ko |
dc.contributor.author | Kim, Kyung Hwan | ko |
dc.contributor.author | Kim, Tae-Shin | ko |
dc.contributor.author | Hong, Seon-Hui | ko |
dc.contributor.author | Kim, Chang Gon | ko |
dc.contributor.author | Kang, Seok-Gu | ko |
dc.contributor.author | Moon, Ju Hyung | ko |
dc.contributor.author | Kim, Eui Hyun | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.contributor.author | Chang, Jong Hee | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.date.accessioned | 2020-01-21T06:20:54Z | - |
dc.date.available | 2020-01-21T06:20:54Z | - |
dc.date.created | 2020-01-21 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.citation | CLINICAL CANCER RESEARCH, v.25, no.8, pp.2549 - 2559 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | http://hdl.handle.net/10203/271671 | - |
dc.description.abstract | Purpose: Immune checkpoint inhibitors (ICI) are used for the treatment of various cancers, but clinical trials of anti-programmed cell death protein 1 (PD-1) with patients with recurrent glioblastoma (GBM) have failed to show clinical benefits. In this study, we examined the differentiation status of CD8(+) tumor-infiltrating lymphocytes (TIL) from patients with primary GBM and their reinvigoration by ICIs to understand the nature of T-cell exhaustion in GBM. Experimental Design: We isolated TILs from 98 patients with newly diagnosed GBM and examined the expression of immune checkpoint receptors and T-cell transcription factors using flow cytometry. TILs were ex vivo stimulated with anti-CD3 in the presence of anti-PD-1 and/or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) and their proliferation assessed. Results: CD8(+) TILs had significantly increased expression of immune checkpoint receptors, including PD-1 and CTLA-4, compared with peripheral blood CD8(+) T cells. Among CD8(+) TILs, PD-1(+) cells exhibited more terminally differentiated phenotypes (i.e., Eomes(hi)T-bet(lo)) than PD-1(-) cells. These data were confirmed by analyzing NY-ESO-1(157)-specific CD8(+) TILs. Evaluating the proliferation of CD8(+) TILs after ex vivo stimulation with anti-CD3 and anti-PD-1, we found that proliferation inversely correlated with the percentage of Eomes(hi)T-bet(lo) cells among PD-1(+) CD8(+) TILs. When anti-CTLA-4 was used in combination with anti-PD-1, an additional increase in CD8(+) TIL proliferation was observed in patients with low percentages of Eomes(hi)T-bet(lo) CD8(+) TILs, who responded well to anti-PD-1 in ex vivo assays, but not in patients with high percentages of Eomes(hi)T-bet(lo) CD8(+) TILs, who did not respond to anti-PD-1. Conclusions: In primary GBM, the differentiation status of CD8(+) TILs determines their reinvigoration ability upon ICI treatment. | - |
dc.language | English | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | Immune Checkpoint Inhibitor-induced Reinvigoration of Tumor-infiltrating CD8(+) T Cells is Determined by Their Differentiation Status in Glioblastoma | - |
dc.type | Article | - |
dc.identifier.wosid | 000464654200022 | - |
dc.identifier.scopusid | 2-s2.0-85064902756 | - |
dc.type.rims | ART | - |
dc.citation.volume | 25 | - |
dc.citation.issue | 8 | - |
dc.citation.beginningpage | 2549 | - |
dc.citation.endingpage | 2559 | - |
dc.citation.publicationname | CLINICAL CANCER RESEARCH | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-18-2564 | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Kim, Tae-Shin | - |
dc.contributor.nonIdAuthor | Kim, Chang Gon | - |
dc.contributor.nonIdAuthor | Kang, Seok-Gu | - |
dc.contributor.nonIdAuthor | Moon, Ju Hyung | - |
dc.contributor.nonIdAuthor | Kim, Eui Hyun | - |
dc.contributor.nonIdAuthor | Chang, Jong Hee | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | PRIMARY BRAIN | - |
dc.subject.keywordPlus | NIVOLUMAB | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | SAFETY | - |
dc.subject.keywordPlus | IMMUNOTHERAPY | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | IPILIMUMAB | - |
dc.subject.keywordPlus | EXHAUSTION | - |
dc.subject.keywordPlus | RESPONSES | - |
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