2021
Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
Backman M, La Fleur L, Kurppa P, Djureinovic D, Elfving H, Brunnström H, Mattsson J, Lindberg A, Pontén V, Eltahir M, Mangsbo S, Gulyas M, Isaksson J, Jirström K, Kärre K, Leandersson K, Mezheyeuski A, Pontén F, Strell C, Lindskog C, Botling J, Micke P. Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer. The Journal Of Pathology 2021, 255: 243-256. PMID: 34339045, DOI: 10.1002/path.5772.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune cell infiltrationHigh immune cell infiltrationCell infiltrationNK cellsImmune classPlasma cellsLow immune cell infiltrationEra of immunotherapyCell lung cancerImmune cell markersTumor mutational loadImmune response-related genesInnate immune responseImmune cell analysisClinicopathologic characteristicsPD-L1Immune activationImmune classificationNSCLC casesImmune patternsLung cancerImmune cellsClinical backgroundImmune response
2019
A clonal expression biomarker associates with lung cancer mortality
Biswas D, Birkbak N, Rosenthal R, Hiley C, Lim E, Papp K, Boeing S, Krzystanek M, Djureinovic D, La Fleur L, Greco M, Döme B, Fillinger J, Brunnström H, Wu Y, Moore D, Skrzypski M, Abbosh C, Litchfield K, Al Bakir M, Watkins T, Veeriah S, Wilson G, Jamal-Hanjani M, Moldvay J, Botling J, Chinnaiyan A, Micke P, Hackshaw A, Bartek J, Csabai I, Szallasi Z, Herrero J, McGranahan N, Swanton C. A clonal expression biomarker associates with lung cancer mortality. Nature Medicine 2019, 25: 1540-1548. PMID: 31591602, PMCID: PMC6984959, DOI: 10.1038/s41591-019-0595-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerClinicopathological risk factorsCell lung cancerLung cancer mortalityPrognostic gene expression signaturesCancer cell proliferationGene expression signaturesCancer mortalityLung cancerRisk factorsExpression-based biomarkersCopy number gainsDisease subtypesClinical descriptorsTranscriptomic biomarkersIndividual tumorsCancer typesDiagnostic precisionMolecular biomarkersExpression signaturesCell proliferationDNA copy number gainsBiomarkersPatientsIntratumor heterogeneityMultiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung
Djureinovic D, Pontén V, Landelius P, Al Sayegh S, Kappert K, Kamali-Moghaddam M, Micke P, Ståhle E. Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung. BMC Cancer 2019, 19: 741. PMID: 31357969, PMCID: PMC6664554, DOI: 10.1186/s12885-019-5943-3.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAgedBlood ProteinsCarcinoembryonic AntigenCarcinoma, Non-Small-Cell LungChemokines, CXCCohort StudiesData AccuracyEarly Detection of CancerFemaleGPI-Linked ProteinsHumansImmunoassayLung NeoplasmsMaleMass ScreeningModels, BiologicalReceptor, ErbB-3ROC CurveSensitivity and SpecificityStatistics, NonparametricVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerProximity extension assayLung adenocarcinomaLung diseaseDisease groupNon-malignant lung diseasesEarly lung cancer detectionCell lung cancerDifferent lung diseasesDifferent plasma levelsMultiplex proximity extension assayHigh clinical relevanceNovel protein markersDifferent plasma concentrationsLocalized diseaseOverall prognosisSurgical resectionNSCLC patientsLung metastasesColorectal cancerLung cancerPlasma levelsTypical carcinoidLung conditionsLAC patientsPrognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
Edlund K, Madjar K, Mattsson J, Djureinovic D, Lindskog C, Brunnström H, Koyi H, Brandén E, Jirström K, Pontén F, Rahnenführer J, Micke P, Hengstler J. Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC. Journal Of Thoracic Oncology 2019, 14: 628-640. PMID: 30639618, DOI: 10.1016/j.jtho.2018.12.022.Peer-Reviewed Original ResearchConceptsPD-L1 positivityOverall survivalLymphocyte infiltrationSmoking historyPD-L1Prognostic associationPlasma cellsProgrammed Death Ligand 1 ExpressionTumor PD-L1 positivityDeath ligand 1 (PD-L1) expressionAssociation of lymphocytePositive immune cellsLigand 1 expressionPD-L1 axisPD-L1 statusMultivariate Cox regressionDeath ligand 1Longer overall survivalForkhead box P3Immune cell infiltrationShorter overall survivalPatients' smoking historyKaplan-Meier plotsCheckpoint inhibitorsNSCLC patients
2018
Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
Djureinovic D, Dodig-Crnković T, Hellström C, Holgersson G, Bergqvist M, Mattsson J, Pontén F, Ståhle E, Schwenk J, Micke P. Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer. Lung Cancer 2018, 125: 157-163. PMID: 30429015, DOI: 10.1016/j.lungcan.2018.09.012.Peer-Reviewed Original ResearchConceptsCancer-testis antigensLung cancer patientsNSCLC patientsCancer patientsNon-small cell lung cancer patientsNon-small cell lung cancerCell lung cancer patientsLin-28 homolog BPresence of autoantibodiesCell lung cancerBenign lung diseasesDetection of autoantibodiesFamily member 3Immune targetsLung diseaseLung cancerNSCLC samplesImmune responseAutoantibodiesBenign groupPatientsBead arrayBead array technologyAntigenMember A (Fam46a) geneAn Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas
Miyashita N, Horie M, Suzuki H, Yoshihara M, Djureinovic D, Persson J, Brunnström H, Lindskog C, Elfving H, Micke P, Saito A, Nagase T. An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1–Positive Lung Adenocarcinomas. Journal Of Thoracic Oncology 2018, 13: 1676-1691. PMID: 30121393, DOI: 10.1016/j.jtho.2018.07.096.Peer-Reviewed Original ResearchConceptsAchaete-scute family bHLH transcription factor 1Transcriptome profilingGenome-wide epigenetic profilingRecent transcriptome profilingGenome-wide methylation analysisFamily bHLH transcription factor 1Cell cycle controlMaster transcriptional regulatorGene expression profilingGlobal DNA hypomethylationLung adenocarcinomaEpigenome featuresTranscription factor 1Transcriptional regulatorsTranscriptional programsCancer Genome AtlasEpigenetic profilingLung adenocarcinoma cellsMolecular featuresExpression profilingCycle controlDNA hypomethylationIntegrative analysisMethylation analysisCell death ligand-1 (PD-L1) protein expressionExpression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer
La Fleur L, Boura V, Alexeyenko A, Berglund A, Pontén V, Mattsson J, Djureinovic D, Persson J, Brunnström H, Isaksson J, Brandén E, Koyi H, Micke P, Karlsson M, Botling J. Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer. International Journal Of Cancer 2018, 143: 1741-1752. PMID: 29667169, DOI: 10.1002/ijc.31545.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesHigher macrophage infiltrationScavenger receptor MARCOPD-L1Macrophage infiltrationNon-small cell lung cancer (NSCLC) cohortMajority of TAMsNon-small cell lung cancerAvailable immune checkpoint inhibitorsCell lung cancer cohortTumor-associated macrophage subsetsImmunosuppressive tumor-associated macrophagesNew immune targetsImmune checkpoint inhibitorsImmune checkpoint moleculesT cell infiltrationDeath ligand 1Cell lung cancerLung cancer cohortSubset of casesImmune response pathwaysExpression of MARCOProtumor phenotypeCheckpoint inhibitorsCheckpoint moleculesMultispectral imaging for quantitative and compartment‐specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients
Mezheyeuski A, Bergsland C, Backman M, Djureinovic D, Sjöblom T, Bruun J, Micke P. Multispectral imaging for quantitative and compartment‐specific immune infiltrates reveals distinct immune profiles that classify lung cancer patients. The Journal Of Pathology 2018, 244: 421-431. PMID: 29282718, DOI: 10.1002/path.5026.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClinical Decision-MakingDeep LearningFluorescent Antibody TechniqueHumansImage Interpretation, Computer-AssistedLung NeoplasmsLymphocyte SubsetsLymphocytes, Tumor-InfiltratingMicroscopy, FluorescencePredictive Value of TestsPrognosisReproducibility of ResultsSequence Analysis, RNATissue Array AnalysisTumor MicroenvironmentConceptsImmune infiltratesImmune markersImmune cellsImmunohistochemical methodsEra of immunotherapyCell lung cancerImmune cell infiltrationLymphocyte subclassesNSCLC casesCell infiltrationLung cancerPatient prognosisImmune responseTissue microarrayCancer tissuesStromal compartmentClinical decisionFurther subpopulationSemiquantitative assessmentConventional immunohistochemistryImmunohistochemistryClinical biopsiesTissue sectionsFoxp3CD4
2017
PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability
Brunnström H, Johansson A, Westbom-Fremer S, Backman M, Djureinovic D, Patthey A, Isaksson-Mettävainio M, Gulyas M, Micke P. PD-L1 immunohistochemistry in clinical diagnostics of lung cancer: inter-pathologist variability is higher than assay variability. Modern Pathology 2017, 30: 1411-1421. PMID: 28664936, DOI: 10.1038/modpathol.2017.59.Peer-Reviewed Original ResearchConceptsPositive tumor cellsTumor cellsLung cancerPD-L1 checkpoint inhibitorsPD-L1 assaysPD-L1 immunohistochemistryCell death 1Squamous cell carcinomaPD-L1 scoresLung cancer casesCheckpoint inhibitorsDeath-1Cell carcinomaClinical studiesCancer casesImmunohistochemical stainingTissue microarrayInterrater variationAntibody 22C3Cutoff levelInter-pathologist variabilityTumor tissueClinical settingSP142Antibody clonesReaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters
Grinberg M, Djureinovic D, Brunnström H, Mattsson J, Edlund K, Hengstler J, La Fleur L, Ekman S, Koyi H, Branden E, Ståhle E, Jirström K, Tracy D, Pontén F, Botling J, Rahnenführer J, Micke P. Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters. Modern Pathology 2017, 30: 964-977. PMID: 28281552, DOI: 10.1038/modpathol.2017.14.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Adhesion Molecule-1Enhancer of Zeste Homolog 2 ProteinGlucose Transporter Type 1HumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsLung NeoplasmsNuclear ProteinsPrognosisThyroid Nuclear Factor 1Tissue Array AnalysisConceptsNon-small cell lung cancerCell lung cancerNon-small cell lung cancer patientsCell lung cancer patientsLung cancer patientsLung cancerBiomarker panelClinical parametersCancer patientsPrognostic associationClinicopathological parametersClinical practicePrognostic modelSurvival predictionProtein expressionBest prognostic modelPrognostic biomarker panelBetter prognostic performanceImmunohistochemistry-based assessmentCorresponding concordance indexProtein biomarkersClinicopathological dataConcordance indexPrognostic performanceTissue microarray
2016
Profiling cancer testis antigens in non–small-cell lung cancer
Djureinovic D, Hallström B, Horie M, Mattsson J, La Fleur L, Fagerberg L, Brunnström H, Lindskog C, Madjar K, Rahnenführer J, Ekman S, Ståhle E, Koyi H, Brandén E, Edlund K, Hengstler J, Lambe M, Saito A, Botling J, Pontén F, Uhlén M, Micke P. Profiling cancer testis antigens in non–small-cell lung cancer. JCI Insight 2016, 1: e86837. PMID: 27699219, PMCID: PMC5033889, DOI: 10.1172/jci.insight.86837.Peer-Reviewed Original ResearchConceptsCell lung cancerLung cancerCancer testisCTA expressionDifferent normal organsProtein expressionCancer Genome AtlasImmunotherapeutic strategiesPrognostic impactNSCLC casesNSCLC tissuesSurvival associationsNew CTANormal organsBiomarker studiesClinical interestCancerGenome AtlasReliable CTACTANSCLCConcurrent expressionRNAseq dataValuable targetStringent criteriaThe Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs
Micke P, Mattsson J, Djureinovic D, Nodin B, Jirström K, Tran L, Jönsson P, Planck M, Botling J, Brunnström H. The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs. Journal Of Thoracic Oncology 2016, 11: 862-872. PMID: 26872818, DOI: 10.1016/j.jtho.2016.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellFemaleHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedNeoplasm StagingNeuroendocrine TumorsPrognosisSmall Cell Lung CarcinomaWorld Health OrganizationConceptsNon-small cell carcinomaPulmonary non-small cell carcinomaCell carcinomaWHO classificationLung tumorsFourth EditionWorld Health Organization classificationLarge cell carcinomaSquamous cell carcinomaThyroid transcription factor-1Cases of adenocarcinomaMost patientsHistological typeAdenocarcinoma groupAdenocarcinomatous differentiationOrganization classificationLung cancerNeuroendocrine tumorsTranscription factor 1Napsin AHistological classificationIHC markersHistopathological classificationImmunohistochemical stainingIHC staining