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Spatial immune heterogeneity in a mouse tumor model after immunotherapy

dc.contributor.authorŠmahel, Michal
dc.contributor.authorJohari, Shweta Dilip
dc.contributor.authorŠmahelová, Jana
dc.contributor.authorPfeiferová, Lucie
dc.contributor.authorNunvář, Jaroslav
dc.date.accessioned2025-03-13T11:15:31Z
dc.date.available2025-03-13T11:15:31Z
dc.date.issued2025
dc.identifier.urihttps://hdl.handle.net/20.500.14178/3034
dc.description.abstractCancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated Apobec1 and Apobec3 genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1111/cas.16421
dc.rightsCreative Commons Uveďte původ-Neužívejte dílo komerčně 4.0 Internationalcs
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.titleSpatial immune heterogeneity in a mouse tumor model after immunotherapyen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by-nc/4.0/legalcode
dc.date.updated2025-03-13T11:15:30Z
dc.subject.keywordDNA repairen
dc.subject.keywordcancer immunotherapyen
dc.subject.keywordintratumoral heterogeneityen
dc.subject.keywordmutationen
dc.subject.keywordtumor microenvironmenten
dc.identifier.eissn1349-7006
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//LX22NPO5103
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//SVV260679
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/GA0/GA/GA19-00816S
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/COOP/COOP
dc.date.embargoStartDate2025-03-13
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1111/cas.16421
dc.identifier.utWos001368374500001
dc.identifier.eidScopus2-s2.0-85211112465
dc.identifier.obd655907
dc.identifier.pubmed39624899
dc.subject.rivPrimary30000::30200::30204
dcterms.isPartOf.nameCancer Science
dcterms.isPartOf.issn1347-9032
dcterms.isPartOf.journalYear2025
dcterms.isPartOf.journalVolume116
dcterms.isPartOf.journalIssue3
uk.faculty.primaryId115
uk.faculty.primaryNamePřírodovědecká fakultacs
uk.faculty.primaryNameFaculty of Scienceen
uk.department.primaryId1034
uk.department.primaryNameKatedra genetiky a mikrobiologiecs
uk.department.primaryNameDepartment of Genetics and Microbiologyen
dc.description.pageRange622-632
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleSpatial immune heterogeneity in a mouse tumor model after immunotherapyen


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