2023
Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Thagaard J, Broeckx G, Page D, Jahangir C, Verbandt S, Kos Z, Gupta R, Khiroya R, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Amgad M, Azmoudeh‐Ardalan F, Badve S, Baharun N, Balslev E, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Dahl A, Portela F, Deman F, Demaria S, Hansen J, Dudgeon S, Ebstrup T, Elghazawy M, Fernandez‐Martín C, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hauberg S, Hewitt S, Hida A, Horlings H, Husain Z, Hytopoulos E, Irshad S, Janssen E, Kahila M, Kataoka T, Kawaguchi K, Kharidehal D, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Kovács A, Laenkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Ly A, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Minhas F, Mittal S, Moore D, Mushtaq S, Nighat H, Papathomas T, Penault‐Llorca F, Perera R, Pinard C, Pinto‐Cardenas J, Pruneri G, Pusztai L, Rahman A, Rajpoot N, Rapoport B, Rau T, Reis‐Filho J, Ribeiro J, Rimm D, Roslind A, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Scott E, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Fineberg S, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, van Diest P, Verghese G, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Zin R, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 498-513. PMID: 37608772, PMCID: PMC10518802, DOI: 10.1002/path.6155.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesTriple-negative breast cancerBreast cancerTIL assessmentHER2-positive breast cancerRoutine clinical managementTIL evaluationTumor-immune interactionsClinical managementDiscordant assessmentsClinical significancePrognostic biomarkerTIL quantificationCancerDaily practicePatientsTrialsTissue patternsAssessmentLymphocytesBiomarkers
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockade
2019
Pathology of spontaneous and immunotherapy‐induced tumor regression in a murine model of melanoma
Blenman KRM, Wang J, Cowper S, Bosenberg M. Pathology of spontaneous and immunotherapy‐induced tumor regression in a murine model of melanoma. Pigment Cell & Melanoma Research 2019, 32: 448-457. PMID: 30702217, PMCID: PMC6500596, DOI: 10.1111/pcmr.12769.Peer-Reviewed Original ResearchConceptsTumor regressionB cellsMelanoma cellsNeutrophil extracellular trapsNeutrophil countAdverse reactionsGeographic necrosisNeutrophil responseExtracellular trapsHistological changesPlasma cellsMurine modelHost responseTumor microenvironmentImmunotherapyNeutrophilsTumorsRegression modelsCellsRegressionLike formationImmunocompetentPlasmablastsEpithelioidMelanoma
2018
Immune Cell and Cell Cluster Phenotyping, Quantitation, and Visualization Using In Silico Multiplexed Images and Tissue Cytometry
Blenman KRM, Bosenberg MW. Immune Cell and Cell Cluster Phenotyping, Quantitation, and Visualization Using In Silico Multiplexed Images and Tissue Cytometry. Cytometry Part A 2018, 95: 399-410. PMID: 30468565, PMCID: PMC6500592, DOI: 10.1002/cyto.a.23668.Peer-Reviewed Original Research
2017
UV‐induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model
Wang J, Perry CJ, Meeth K, Thakral D, Damsky W, Micevic G, Kaech S, Blenman K, Bosenberg M. UV‐induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell & Melanoma Research 2017, 30: 428-435. PMID: 28379630, PMCID: PMC5820096, DOI: 10.1111/pcmr.12591.Peer-Reviewed Original ResearchConceptsHigh somatic mutation burdenSomatic mutation burdenT cellsMutation burdenAnti-PD-1 therapyFunctional T cell responsesImmune checkpoint inhibitionAntitumor immune responseCD8 T cellsT cell responsesMouse melanoma modelCell numberSomatic mutationsMouse melanoma cell lineMelanoma cell linesTumor challengeAntitumor responseCheckpoint inhibitionImmune responseMelanoma modelHigh dosesImmune systemCell responsesMelanomas exhibitTumors
2006
IL-10 regulation of lupus in the NZM2410 murine model
Blenman KR, Duan B, Xu Z, Wan S, Atkinson MA, Flotte TR, Croker BP, Morel L. IL-10 regulation of lupus in the NZM2410 murine model. Laboratory Investigation 2006, 86: 1136-1148. PMID: 16924244, DOI: 10.1038/labinvest.3700468.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearB-Lymphocyte SubsetsCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGene Expression RegulationGene Transfer TechniquesGenetic Predisposition to DiseaseGenetic TherapyInterleukin-10KidneyLupus Erythematosus, SystemicLupus NephritisMiceMice, CongenicMice, Inbred C57BLMice, Inbred NZBReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSpecific Pathogen-Free OrganismsSpleenConceptsIL-10T cell activationMurine modelB cellsElevated IL-10IL-10 levelsSubset of CD4Auto-antibody productionB-cell phenotypeMajor effector armMonths of ageIL-10 regulationMuscle gene deliveryClinical nephritisSLE patientsRegulatory cellsProinflammatory responseSystemic autoimmunityRegulatory cytokinesEffector armSLE susceptibility lociT cellsC57BL/6 backgroundMyeloid cellsCongenic model
2004
Aberrant signaling in the TNFα/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse
Blenman KR, Bahjat FR, Moldawer LL, Morel L. Aberrant signaling in the TNFα/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse. Clinical Immunology 2004, 110: 124-133. PMID: 15003809, DOI: 10.1016/j.clim.2003.09.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDApoptosisAspartate AminotransferasesCaspase 3CaspasesCytotoxicity Tests, ImmunologicFemaleGalactosamineIn Situ Nick-End LabelingInterleukin-10Interleukin-6LipopolysaccharidesLiverLupus Erythematosus, SystemicMaleMiceMice, CongenicMice, Inbred C57BLReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ISignal TransductionTumor Necrosis Factor-alpha
2001
The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes
Morel L, Blenman K, Croker B, Wakeland E. The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 1787-1792. PMID: 11172029, PMCID: PMC29335, DOI: 10.1073/pnas.98.4.1787.Peer-Reviewed Original ResearchConceptsSusceptibility lociComplex trait lociCluster of genesFine-mapping analysisSystemic lupus erythematosus susceptibility lociTrait lociGenomic intervalsEpistatic interactionsModifier lociChromosomal regionsGenetic complexityAdditional lociLociCongenic analysisSusceptibility genesGenesCongenic intervalChromatinCellular characteristicsCell functionMapping analysisMultiple human studiesRelated functionsAutoimmune phenotypeSle1
2000
Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains
Morel L, Croker B, Blenman K, Mohan C, Huang G, Gilkeson G, Wakeland E. Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 6670-6675. PMID: 10841565, PMCID: PMC18697, DOI: 10.1073/pnas.97.12.6670.Peer-Reviewed Original ResearchConceptsLoss of toleranceSystemic autoimmunityLupus-prone NZM2410 mouseFull disease expressionSevere systemic autoimmunitySystemic lupus erythematosusLupus-prone strainsLupus susceptibility genesFatal glomerulonephritisFatal lupusSevere glomerulonephritisLupus erythematosusKidney failureT cellsMurine strainsC57BL/6 backgroundB cellsAutoimmune phenotypeDisease pathogenesisNZM2410 miceTherapeutic interventionsFatal diseaseDisease expressionCongenic dissectionNuclear antigen
1996
Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain
Morel L, Yu Y, Blenman KR, Caldwell RA, Wakeland EK. Production of congenic mouse strains carrying genomic intervals containing SLE-susceptibility genes derived from the SLE-prone NZM2410 strain. Mammalian Genome 1996, 7: 335-339. PMID: 8661718, DOI: 10.1007/s003359900098.Peer-Reviewed Original ResearchConceptsGenomic intervalsSLE susceptibility genesSingle genomic intervalComplex polygenic traitCongenic strainsSLE susceptibility lociGenetic interactionsPositional cloningPolygenic traitGenetic crossesInterval mappingPhenotypic dataGenetic analysisNZM2410 mouse modelNZM2410 strainComponent phenotypesChromosome 17Congenic miceGenesMarker-assisted selection protocolSusceptibility allelesPolygenic modelComplex pathogenic mechanismsSelection protocolPathogenic mechanisms