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Dysregulation of T FH-B-T RM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer

DC Field Value Language
dc.contributor.author김혜련-
dc.contributor.author박성용-
dc.contributor.author심효섭-
dc.contributor.author김혜련-
dc.contributor.author박성용-
dc.contributor.author심효섭-
dc.date.accessioned2021-12-28T16:54:06Z-
dc.date.available2021-12-28T16:54:06Z-
dc.date.issued2021-10-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/186842-
dc.description.abstractPatients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations exhibit an unfavorable response to PD-1 inhibitor through unclear mechanisms. Hypothesizing that EGFR mutations alter tumor-immune interactions, we compare tumor-infiltrating lymphocytes between EGFR mutant (EGFR-MT) and wild type (EGFR-WT) tumors through single-cell transcriptomic analysis. We find that B cells, CXCL13-producing follicular helper CD4+ T (TFH)-like cells, and tissue-resident memory CD8+ T (TRM)-like cells decreased in EGFR-MT tumors. The NOTCH-RBPJ regulatory network, which is vital for persistence of TRM state, is perturbed, and the interactions between TFH and B cells through the CXCL13-CXCR5 axis disappear in EGFR-MT tumors. Notably, the proportion of TRM-like cells is predictive for anti-PD-1 response in NSCLC. Our findings suggest that the impairment of TFH-B-TRM cooperation in tertiary lymphoid structure formation, accompanied by the dysregulation of TRM homeostasis and the loss of TFH-B crosstalk, underlies unfavorable anti-PD-1 response in EGFR-MT lung tumors.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHB-Lymphocytes-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung / genetics-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung / metabolism-
dc.subject.MESHChemokine CXCL13 / metabolism-
dc.subject.MESHErbB Receptors / genetics*-
dc.subject.MESHErbB Receptors / metabolism*-
dc.subject.MESHFemale-
dc.subject.MESHHomeostasis-
dc.subject.MESHHumans-
dc.subject.MESHLung Neoplasms / genetics*-
dc.subject.MESHLung Neoplasms / metabolism*-
dc.subject.MESHLung Neoplasms / pathology-
dc.subject.MESHLymphocyte Cooperation / physiology*-
dc.subject.MESHLymphocytes, Tumor-Infiltrating-
dc.subject.MESHMale-
dc.subject.MESHMutation-
dc.subject.MESHReceptors, CXCR5 / metabolism-
dc.titleDysregulation of T FH-B-T RM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorJae-Won Cho-
dc.contributor.googleauthorSeyeon Park-
dc.contributor.googleauthorGamin Kim-
dc.contributor.googleauthorHeonjong Han-
dc.contributor.googleauthorHyo Sup Shim-
dc.contributor.googleauthorSunhye Shin-
dc.contributor.googleauthorYong-Soo Bae-
dc.contributor.googleauthorSeong Yong Park-
dc.contributor.googleauthorSang-Jun Ha-
dc.contributor.googleauthorInsuk Lee-
dc.contributor.googleauthorHye Ryun Kim-
dc.identifier.doi10.1038/s41467-021-26362-0-
dc.contributor.localIdA01166-
dc.contributor.localIdA01508-
dc.contributor.localIdA02219-
dc.contributor.localIdA01166-
dc.contributor.localIdA01508-
dc.contributor.localIdA02219-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid34663810-
dc.contributor.alternativeNameKim, Hye Ryun-
dc.contributor.affiliatedAuthor김혜련-
dc.contributor.affiliatedAuthor박성용-
dc.contributor.affiliatedAuthor심효섭-
dc.contributor.affiliatedAuthor김혜련-
dc.contributor.affiliatedAuthor박성용-
dc.contributor.affiliatedAuthor심효섭-
dc.citation.volume12-
dc.citation.number1-
dc.citation.startPage6068-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.12(1) : 6068, 2021-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers

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