Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이수진 | * |
dc.date.accessioned | 2022-02-22T16:31:02Z | - |
dc.date.available | 2022-02-22T16:31:02Z | - |
dc.date.issued | 2022 | * |
dc.identifier.issn | 1756-994X | * |
dc.identifier.other | OAK-30803 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/260591 | - |
dc.description.abstract | Background: A limited number of studies have characterized genomic properties of hepatocellular carcinoma (HCC) patients in response to anti-PD-1 immunotherapy. Methods: Herein, we performed comprehensive molecular characterization of immediate (D-42 to D-1) pre-treatment tumor biopsy specimens from 60 patients with sorafenib-failed HCC in a single-arm prospective phase II trial of pembrolizumab. Objective response rate was the primary efficacy endpoint. We used whole-exome sequencing, RNA sequencing, and correlative analysis. In addition, we performed single-cell RNA sequencing using peripheral blood mononuclear cells. Results: The overall response rate of pembrolizumab in sorafenib-failed HCC patients was 10% ([6/60] 95% CI, 2.4–17.6). In a univariate analysis using clinicopathological features, female gender, PD-L1 positivity, and low neutrophil-to-lymphocyte ratio (NLR) were identified as contributing factors to pembrolizumab response. Somatic mutations in CTNNB1 and genomic amplifications in MET were found only in non-responders. Transcriptional profiles through RNA sequencing identified that pembrolizumab responders demonstrated T cell receptor (TCR) signaling activation with expressions of MHC genes, indicating increased levels of T cell cytotoxicity. In single-cell sequencing from 10 pre- and post-treatment peripheral blood mononuclear cells (PBMCs), patients who achieved a partial response or stable disease exhibited immunological shifts toward cytotoxic CD8+ T cells. Conversely, patients with progressive disease showed an increased number of both CD14+ and CD16+ monocytes and activation of neutrophil-associated pathways. Conclusions: Taken together, HCC patients with infiltration of cytotoxic T cells, along with increased active circulating CD8+ T cells during pembrolizumab treatment and down-regulation of neutrophil-associated markers, significantly benefited from pembrolizumab treatment. Trial registration: NCT#03163992 (first posted: May 23, 2017). © 2021, The Author(s). | * |
dc.language | English | * |
dc.publisher | BioMed Central Ltd | * |
dc.subject | Biomarkers | * |
dc.subject | Carcinoma | * |
dc.subject | Hepatocellular | * |
dc.subject | Pembrolizumab | * |
dc.subject | Tumor | * |
dc.title | Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial | * |
dc.type | Article | * |
dc.relation.issue | 1 | * |
dc.relation.volume | 14 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | Genome Medicine | * |
dc.identifier.doi | 10.1186/s13073-021-00995-8 | * |
dc.identifier.wosid | WOS:000739381200001 | * |
dc.identifier.scopusid | 2-s2.0-85122283060 | * |
dc.author.google | Hong J.Y. | * |
dc.author.google | Cho H.J. | * |
dc.author.google | Sa J.K. | * |
dc.author.google | Liu X. | * |
dc.author.google | Ha S.Y. | * |
dc.author.google | Lee T. | * |
dc.author.google | Kim H. | * |
dc.author.google | Kang W. | * |
dc.author.google | Sinn D.H. | * |
dc.author.google | Gwak G.-Y. | * |
dc.author.google | Choi M.S. | * |
dc.author.google | Lee J.H. | * |
dc.author.google | Koh K.C. | * |
dc.author.google | Paik S.W. | * |
dc.author.google | Park H.C. | * |
dc.author.google | Kang T.W. | * |
dc.author.google | Rhim H. | * |
dc.author.google | Lee S.J. | * |
dc.author.google | Cristescu R. | * |
dc.author.google | Lee J. | * |
dc.author.google | Paik Y.H. | * |
dc.author.google | Lim H.Y. | * |
dc.contributor.scopusid | 이수진(55931708700) | * |
dc.date.modifydate | 20231214111834 | * |