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 Field | Value | Language |
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dc.contributor.author | Hong, Jung Yong | - |
dc.contributor.author | Cho, Hee Jin | - |
dc.contributor.author | Sa, Jason K. | - |
dc.contributor.author | Liu, Xiaoqiao | - |
dc.contributor.author | Ha, Sang Yun | - |
dc.contributor.author | Lee, Taehyang | - |
dc.contributor.author | Kim, Hajung | - |
dc.contributor.author | Kang, Wonseok | - |
dc.contributor.author | Sinn, Dong Hyun | - |
dc.contributor.author | Gwak, Geum-Youn | - |
dc.contributor.author | Choi, Moon Seok | - |
dc.contributor.author | Lee, Joon Hyeok | - |
dc.contributor.author | Koh, Kwang Cheol | - |
dc.contributor.author | Paik, Seung Woon | - |
dc.contributor.author | Park, Hee Chul | - |
dc.contributor.author | Kang, Tae Wook | - |
dc.contributor.author | Rhim, Hyunchul | - |
dc.contributor.author | Lee, Su Jin | - |
dc.contributor.author | Cristescu, Razvan | - |
dc.contributor.author | Lee, Jeeyun | - |
dc.contributor.author | Paik, Yong Han | - |
dc.contributor.author | Lim, Ho Yeong | - |
dc.date.accessioned | 2022-02-22T18:42:04Z | - |
dc.date.available | 2022-02-22T18:42:04Z | - |
dc.date.created | 2022-02-11 | - |
dc.date.issued | 2022-01-06 | - |
dc.identifier.issn | 1756-994X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/136530 | - |
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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.subject | C-MET | - |
dc.subject | HYPOXIC CONDITIONS | - |
dc.subject | MONOTHERAPY | - |
dc.subject | RESISTANCE | - |
dc.subject | LANDSCAPE | - |
dc.subject | RESPONSES | - |
dc.subject | EFFICACY | - |
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.contributor.affiliatedAuthor | Sa, Jason K. | - |
dc.identifier.doi | 10.1186/s13073-021-00995-8 | - |
dc.identifier.scopusid | 2-s2.0-85122283060 | - |
dc.identifier.wosid | 000739381200001 | - |
dc.identifier.bibliographicCitation | GENOME MEDICINE, v.14, no.1 | - |
dc.relation.isPartOf | GENOME MEDICINE | - |
dc.citation.title | GENOME MEDICINE | - |
dc.citation.volume | 14 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.subject.keywordPlus | C-MET | - |
dc.subject.keywordPlus | HYPOXIC CONDITIONS | - |
dc.subject.keywordPlus | MONOTHERAPY | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | LANDSCAPE | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordAuthor | Carcinoma | - |
dc.subject.keywordAuthor | Hepatocellular | - |
dc.subject.keywordAuthor | Pembrolizumab | - |
dc.subject.keywordAuthor | Biomarkers | - |
dc.subject.keywordAuthor | Tumor | - |
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