Targeting the NANOG/HDAC1 axis reverses resistance to PD-1 blockade by reinvigorating the antitumor immunity cycle
DC Field | Value | Language |
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dc.contributor.author | Oh, Se Jin | - |
dc.contributor.author | Lee, Hyo-Jung | - |
dc.contributor.author | Song, Kwon-Ho | - |
dc.contributor.author | Kim, Suyeon | - |
dc.contributor.author | Cho, Eunho | - |
dc.contributor.author | Lee, Jaeyoon | - |
dc.contributor.author | Bosenberg, Marcus W. | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.date.accessioned | 2022-06-10T21:40:27Z | - |
dc.date.available | 2022-06-10T21:40:27Z | - |
dc.date.created | 2022-06-09 | - |
dc.date.issued | 2022-03-15 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/141902 | - |
dc.description.abstract | Immune checkpoint blockade (ICB) therapy has shifted the paradigm for cancer treatment. However, the majority of patients lack effective responses because of the emergence of immune-refractory tumors that disrupt the amplification of antitumor immunity. Therefore, the identification of clinically available targets that restrict antitumor immunity is required to develop potential combination therapies. Here, using transcriptomic data on patients with cancer treated with programmed cell death protein 1 (PD-1) therapy and newly established mouse preclinical anti-PD-1 therapy-refractory models, we identified NANOG as a factor restricting the amplification of the antitumor immunity cycle, thereby contributing to the immune-refractory feature of the tumor microenvironment (TME). Mechanistically, NANOG induced insufficient T cell infiltration and resistance to CTL-mediated killing via the histone deacetylase 1-dependent (HDAC1-dependent) regulation of CXCL10 and MCL1, respectively. Importantly, HDAC1 inhibition using an actionable agent sensitized NANOG(hi) immune-refractory tumors to PD-1 blockade by reinvigorating the antitumor immunity cycle. Thus, our findings implicate the NANOG/HDAC1 axis as a central molecular target for controlling immune-refractory tumors and provide a rationale for combining HDAC inhibitors to reverse the refractoriness of tumors to ICB therapy. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | - |
dc.subject | HISTONE DEACETYLASE INHIBITORS | - |
dc.subject | DENDRITIC CELLS | - |
dc.subject | CANCER | - |
dc.subject | PROMOTES | - |
dc.subject | NANOG | - |
dc.subject | GENE | - |
dc.subject | EXPRESSION | - |
dc.subject | NIVOLUMAB | - |
dc.subject | TRAFFICKING | - |
dc.subject | ACTIVATION | - |
dc.title | Targeting the NANOG/HDAC1 axis reverses resistance to PD-1 blockade by reinvigorating the antitumor immunity cycle | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae Woo | - |
dc.identifier.doi | 10.1172/JCI147908 | - |
dc.identifier.scopusid | 2-s2.0-85126490523 | - |
dc.identifier.wosid | 000772266400007 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL INVESTIGATION, v.132, no.6 | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.citation.title | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.citation.volume | 132 | - |
dc.citation.number | 6 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | HISTONE DEACETYLASE INHIBITORS | - |
dc.subject.keywordPlus | DENDRITIC CELLS | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | PROMOTES | - |
dc.subject.keywordPlus | NANOG | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | NIVOLUMAB | - |
dc.subject.keywordPlus | TRAFFICKING | - |
dc.subject.keywordPlus | ACTIVATION | - |
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