DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Hyung-Don | ko |
dc.contributor.author | Park, Seongyeol | ko |
dc.contributor.author | Jeong, Seongju | ko |
dc.contributor.author | Lee, Yong Joon | ko |
dc.contributor.author | Lee, Hoyoung | ko |
dc.contributor.author | Kim, Chang Gon | ko |
dc.contributor.author | Kim, Kyung Hwan | ko |
dc.contributor.author | Hong, Seung-Mo | ko |
dc.contributor.author | Lee, Jung-Yun | ko |
dc.contributor.author | Kim, Sunghoon | ko |
dc.contributor.author | Kim, Hong Kwan | ko |
dc.contributor.author | Min, Byung Soh | ko |
dc.contributor.author | Chang, Jong Hee | ko |
dc.contributor.author | Ju, Young Seok | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Song, Gi-Won | ko |
dc.contributor.author | Hwang, Shin | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.date.accessioned | 2020-06-19T07:20:10Z | - |
dc.date.available | 2020-06-19T07:20:10Z | - |
dc.date.created | 2019-11-04 | - |
dc.date.issued | 2020-03 | - |
dc.identifier.citation | HEPATOLOGY, v.71, no.3, pp.955 - 971 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10203/274721 | - |
dc.description.abstract | Background and Aims Targeting costimulatory receptors with agonistic antibodies is a promising cancer immunotherapy option. We aimed to investigate costimulatory receptor expression, particularly 4-1BB (CD137 or tumor necrosis factor receptor superfamily member 9), on tumor-infiltrating CD8(+) T cells (CD8(+) tumor-infiltrating lymphocytes [TILs]) and its association with distinct T-cell activation features among exhausted CD8(+) TILs in hepatocellular carcinoma (HCC). Approach and Results Tumor tissues, adjacent nontumor tissues, and peripheral blood were collected from HCC patients undergoing surgical resection (n = 79). Lymphocytes were isolated and used for multicolor flow cytometry, RNA-sequencing, and in vitro functional restoration assays. Among the examined costimulatory receptors, 4-1BB was most prominently expressed on CD8(+) TILs. 4-1BB expression was almost exclusively detected on CD8(+) T cells in the tumor-especially on programmed death 1 (PD-1)(high) cells and not PD-1(int) and PD-1(neg) cells. Compared to PD-1(int) and 4-1BB(neg)PD-1(high) CD8(+) TILs, 4-1BB(pos)PD-1(high) CD8(+) TILs exhibited higher levels of tumor reactivity and T-cell activation markers and significant enrichment for T-cell activation gene signatures. Per-patient analysis revealed positive correlations between percentages of 4-1BB(pos) cells among CD8(+) TILs and levels of parameters of tumor reactivity and T-cell activation. Among highly exhausted PD-1(high) CD8(+) TILs, 4-1BB(pos) cells harbored higher proportions of cells with proliferative and reinvigoration potential. Our 4-1BB-related gene signature predicted survival outcomes of HCC patients in the The Cancer Genome Atlas cohort. 4-1BB agonistic antibodies enhanced the function of CD8(+) TILs and further enhanced the anti-PD-1-mediated reinvigoration of CD8(+) TILs, especially in cases showing high levels of T-cell activation. Conclusion 4-1BB expression on CD8(+) TILs represents a distinct activation state among highly exhausted CD8(+) T cells in HCC. 4-1BB costimulation with agonistic antibodies may be a promising strategy for treating HCCs exhibiting prominent T-cell activation. | - |
dc.language | English | - |
dc.publisher | WILEY | - |
dc.title | 4-1BB Delineates Distinct Activation Status of Exhausted Tumor-Infiltrating CD8(+) T Cells in Hepatocellular Carcinoma | - |
dc.type | Article | - |
dc.identifier.wosid | 000491386400001 | - |
dc.identifier.scopusid | 2-s2.0-85072232471 | - |
dc.type.rims | ART | - |
dc.citation.volume | 71 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 955 | - |
dc.citation.endingpage | 971 | - |
dc.citation.publicationname | HEPATOLOGY | - |
dc.identifier.doi | 10.1002/hep.30881 | - |
dc.contributor.localauthor | Ju, Young Seok | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.nonIdAuthor | Hong, Seung-Mo | - |
dc.contributor.nonIdAuthor | Lee, Jung-Yun | - |
dc.contributor.nonIdAuthor | Kim, Sunghoon | - |
dc.contributor.nonIdAuthor | Kim, Hong Kwan | - |
dc.contributor.nonIdAuthor | Min, Byung Soh | - |
dc.contributor.nonIdAuthor | Chang, Jong Hee | - |
dc.contributor.nonIdAuthor | Song, Gi-Won | - |
dc.contributor.nonIdAuthor | Hwang, Shin | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CANCER-IMMUNOTHERAPY | - |
dc.subject.keywordPlus | CO-STIMULATION | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | MELANOMA | - |
dc.subject.keywordPlus | ANTIBODY | - |
dc.subject.keywordPlus | SUBSETS | - |
dc.subject.keywordPlus | CD137 | - |
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