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Comprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer

DC FieldValueLanguage
dc.contributor.author김혜련-
dc.contributor.author심효섭-
dc.contributor.author윤미란-
dc.contributor.author임선민-
dc.contributor.author장미-
dc.contributor.author조병철-
dc.contributor.author표경호-
dc.contributor.author홍민희-
dc.date.accessioned2020-12-01T16:59:32Z-
dc.date.available2020-12-01T16:59:32Z-
dc.date.issued2020-07-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180076-
dc.description.abstractBackground: EML4-ALK is a distinct molecular entity that is highly sensitive to ALK tyrosine kinase inhibitors (TKIs). Immune checkpoint inhibitors (ICIs) have not proved efficacy in ALK-positive non-small cell lung cancer so far. In this study, we performed a mouse clinical trial using EML4-ALK transgenic mice model to comprehensively investigate immunomodulatory effects of ALK TKI and to investigate the mechanisms of resistance to ICIs. Methods: EML4-ALK transgenic mice were randomized to three treatment arms (arm A: antiprogrammed death cell protein-1 (PD-1), arm B: ceritinib, arm C: anti-PD-1 and ceritinib), and tumor response was evaluated using MRI. Progression-free survival and overall survival were measured to compare the efficacy. Flow cytometry, multispectral imaging, whole exome sequencing and RNA sequencing were performed from tumors obtained before and after drug resistance. Results: Mouse clinical trial revealed that anti-PD-1 therapy was ineffective, and the efficacy of ceritinib and anti-PD-1 combination was not more effective than ceritinib alone in the first line. Dynamic changes in immune cells and cytokines were observed following each treatment, while changes in T lymphocytes were not prominent. A closer look at the tumor immune microenvironment before and after ceritinib resistance revealed increased regulatory T cells and programmed death-ligand 1 (PD-L1)-expressing cells both in the tumor and the stroma. Despite the increase of PD-L1 expression, these findings were not accompanied by increased effector T cells which mediate antitumor immune responses. Conclusions: ALK-positive tumors progressing on ceritinib is not immunogenic enough to respond to immune checkpoint inhibitors.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherBioMed Central-
dc.relation.isPartOfJOURNAL FOR IMMUNOTHERAPY OF CANCER-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleComprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorKyoung-Ho Pyo-
dc.contributor.googleauthorSun Min Lim-
dc.contributor.googleauthorChae-Won Park-
dc.contributor.googleauthorHa-Ni Jo-
dc.contributor.googleauthorJae Hwan Kim-
dc.contributor.googleauthorMi-Ran Yun-
dc.contributor.googleauthorDohee Kim-
dc.contributor.googleauthorChun-Feng Xin-
dc.contributor.googleauthorWongeun Lee-
dc.contributor.googleauthorBianca Gheorghiu-
dc.contributor.googleauthorMin Hee Hong-
dc.contributor.googleauthorHye Ryun Kim-
dc.contributor.googleauthorHyo Sup Shim-
dc.contributor.googleauthorMi Jang-
dc.contributor.googleauthorSung Sook Lee-
dc.contributor.googleauthorByoung Chul Cho-
dc.identifier.doi10.1136/jitc-2020-000970-
dc.contributor.localIdA01166-
dc.contributor.localIdA02219-
dc.contributor.localIdA02219-
dc.contributor.localIdA04776-
dc.contributor.localIdA04776-
dc.contributor.localIdA03369-
dc.contributor.localIdA03369-
dc.contributor.localIdA05841-
dc.contributor.localIdA05841-
dc.contributor.localIdA03822-
dc.contributor.localIdA03822-
dc.contributor.localIdA04809-
dc.contributor.localIdA04809-
dc.contributor.localIdA04393-
dc.contributor.localIdA04393-
dc.relation.journalcodeJ03617-
dc.identifier.pmid32727812-
dc.subject.keywordimmunotherapy-
dc.contributor.alternativeNameKim, Hye Ryun-
dc.contributor.affiliatedAuthor김혜련-
dc.contributor.affiliatedAuthor심효섭-
dc.contributor.affiliatedAuthor심효섭-
dc.contributor.affiliatedAuthor윤미란-
dc.contributor.affiliatedAuthor윤미란-
dc.contributor.affiliatedAuthor임선민-
dc.contributor.affiliatedAuthor임선민-
dc.contributor.affiliatedAuthor장미-
dc.contributor.affiliatedAuthor장미-
dc.contributor.affiliatedAuthor조병철-
dc.contributor.affiliatedAuthor조병철-
dc.contributor.affiliatedAuthor표경호-
dc.contributor.affiliatedAuthor표경호-
dc.contributor.affiliatedAuthor홍민희-
dc.contributor.affiliatedAuthor홍민희-
dc.citation.volume8-
dc.citation.number2-
dc.citation.startPagee000970-
dc.identifier.bibliographicCitationJOURNAL FOR IMMUNOTHERAPY OF CANCER, Vol.8(2) : e000970, 2020-07-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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