2024
Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer
Jahangir C, Page D, Broeckx G, Gonzalez C, Burke C, Murphy C, Reis‐Filho J, Ly A, Harms P, Gupta R, Vieth M, Hida A, Kahila M, Kos Z, van Diest P, Verbandt S, Thagaard J, Khiroya R, Abduljabbar K, Haab G, Acs B, Adams S, Almeida J, Alvarado‐Cabrero I, Azmoudeh‐Ardalan F, Badve S, Baharun N, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Portela F, Deman F, Demaria S, Dudgeon S, Elghazawy M, Fernandez‐Martín C, Fineberg S, Fox S, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hewitt S, Horlings H, Husain Z, Irshad S, Janssen E, Kataoka T, Kawaguchi K, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Akturk G, Scott E, Kovács A, Lænkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Kharidehal D, 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, Rajpoot N, Rapoport B, Rau T, Ribeiro J, Rimm D, Vincent‐Salomon A, Saltz J, Sayed S, Hytopoulos E, Mahon S, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, Verghese G, Viale G, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Stovgaard E, Salgado R, Gallagher W, Rahman A. Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2024, 262: 271-288. PMID: 38230434, PMCID: PMC11288342, DOI: 10.1002/path.6238.Peer-Reviewed Original ResearchConceptsImmune profileInternational Immuno-Oncology Biomarker Working GroupIdentification of clinically relevant biomarkersField of immuno-oncologyBiomarker Working GroupManagement of cancer patientsImmune profiling of tumorsClinical trial perspectiveTranslational implicationsProfiling of tumorsIndividual tumor cellsPredicting disease prognosisClinically relevant biomarkersSubtypes of cancerImmuno-oncologyTumor microenvironmentMultiplex immunohistochemistryTreatment responseTumor cellsBreast cancerTumor samplesCancer patientsTreatment choiceDisease prognosisRelevant biomarkers
2023
Initial interactions with the FDA on developing a validation dataset as a medical device development tool
Hart S, Garcia V, Dudgeon S, Hanna M, Li X, Blenman K, Elfer K, Ly A, Salgado R, Saltz J, Gupta R, Hytopoulos E, Larsimont D, Lennerz J, Gallas B. Initial interactions with the FDA on developing a validation dataset as a medical device development tool. The Journal Of Pathology 2023, 261: 378-384. PMID: 37794720, PMCID: PMC10841854, DOI: 10.1002/path.6208.Peer-Reviewed Original ResearchSpatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Page D, Broeckx G, Jahangir C, Verbandt S, Gupta R, Thagaard J, Khiroya R, Kos Z, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Azmoudeh‐Ardalan F, Badve S, Baharun N, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Portela F, Deman F, Demaria S, Dudgeon S, Elghazawy M, Ely S, Fernandez‐Martín C, Fineberg S, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hardas A, Hart S, Hartman J, 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, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, 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, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 514-532. PMID: 37608771, PMCID: PMC11288334, DOI: 10.1002/path.6165.Peer-Reviewed Original ResearchPitfalls 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 patternsAssessmentLymphocytesBiomarkersA review of the impact of energy balance on triple-negative breast cancer
Akingbesote N, Owusu D, Liu R, Cartmel B, Ferrucci L, Zupa M, Lustberg M, Sanft T, Blenman K, Irwin M, Perry R. A review of the impact of energy balance on triple-negative breast cancer. JNCI Monographs 2023, 2023: 104-124. PMID: 37139977, DOI: 10.1093/jncimonographs/lgad011.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTriple-negative breast cancerInterventional studyBreast cancerCancer treatmentClinical interventional studyClinical observationalImmune activationCancer outcomesCancer careClinical studiesOverall healthEnergy intakeNarrative reviewCancer cellsEnergy expenditureCancerTreatmentEnergy balanceOutcomesExerciseReviewDetrimental effectsImmunotherapyStudyIntake
2022
PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer
Rozenblit M, Blenman K, Harigopal M, Reisenbichler E, Singh K, Qing T, Ibrahim E, Ramkissoon S, Asmelash S, Lin HK, Roberts M, Ross J, Huang RSP, Pusztai L. PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer. Breast Cancer Research And Treatment 2022, 196: 221-227. PMID: 36028784, DOI: 10.1007/s10549-022-06712-2.Peer-Reviewed Original ResearchConceptsPD-L1 positivityPD-L1 protein expressionPD-L1 expressionGrade 3 cancersPD-L1TIL scoreTumor gradeMultivariate analysisHigher PD-L1 positivityTumor-infiltrating lymphocyte countsConclusionPD-L1 expressionProtein expressionPD-L1 immunohistochemistryChi-square testResultsPD-L1T1 cancersLymphocyte countT3 tumorsIndependent predictorsTumor sizeLarge tumorsPositivity rateCell positivityBreast cancerGrade 2Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm DL, Pusztai L. Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. Clinical Cancer Research 2022, 28: 3720-3728. PMID: 35903931, PMCID: PMC9444984, DOI: 10.1158/1078-0432.ccr-22-0862.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsTriple-negative breast cancerNon-AA patientsEvent-free survivalPhase I/II clinical trialsClinical trialsNeoadjuvant chemotherapyOverall survivalAA patientsEarly-stage triple-negative breast cancerIncidence of irAEsPathologic complete response rateSignificant associationMultivariate logistic regression analysisTumor-infiltrating lymphocyte countsComplete response ratePrimary efficacy endpointPD-L1 statusProportional hazards modelLogistic regression analysisAfrican American womenEFS ratesNeoadjuvant immunotherapyEfficacy endpointAdverse eventsTriple-negative breast cancer prevalence in Africa: a systematic review and meta-analysis
Hercules SM, Alnajar M, Chen C, Mladjenovic SM, Shipeolu BA, Perkovic O, Pond GR, Mbuagbaw L, Blenman KR, Daniel JM. Triple-negative breast cancer prevalence in Africa: a systematic review and meta-analysis. BMJ Open 2022, 12: e055735. PMID: 35623750, PMCID: PMC9150263, DOI: 10.1136/bmjopen-2021-055735.Peer-Reviewed Original ResearchConceptsTNBC frequencySystematic reviewReceptor statusAggressive triple-negative breast cancer subtypeTriple-negative breast cancer subtypeER/PR statusASCO/CAP guidelinesBreast cancer tissue samplesCertainty of evidenceInverse variance methodRisk of biasBreast cancer prevalenceBreast cancer subtypesAfrican Journals OnlineCancer tissue samplesWeb of ScienceRecommendations AssessmentGRADE approachPR statusCAP guidelinesEligible participantsSELECTING STUDIESHER2 statusCancer prevalenceModified assessment toolAnalysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer
Hercules SM, Liu X, Bassey-Archibong BBI, Skeete DHA, Smith Connell S, Daramola A, Banjo AA, Ebughe G, Agan T, Ekanem IO, Udosen J, Obiorah C, Ojule AC, Misauno MA, Dauda AM, Egbujo EC, Hercules JC, Ansari A, Brain I, MacColl C, Xu Y, Jin Y, Chang S, Carpten JD, Bédard A, Pond GR, Blenman KRM, Manojlovic Z, Daniel JM. Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer. Cancer Causes & Control 2022, 33: 831-841. PMID: 35384527, PMCID: PMC9085672, DOI: 10.1007/s10552-022-01574-x.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingNegative breast cancerBreast cancerPurposeTriple-negative breast cancerAggressive breast cancer subtypeTriple-negative breast cancerMultisite cross-sectional studyExome sequencingFormalin-fixed paraffin-embedded samplesMutational profileCross-sectional studyBreast cancer subtypesNon-tumor samplesParaffin-embedded samplesCancer Genome AtlasTNBC casesPoor survivalHigh prevalenceTNBC samplesHigh-frequency alterationsAmerican cohortConclusionThis studyFrequency of mutationsCancer subtypesNigerian womenPredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycleStrategies to mitigate the toxicity of cancer therapeutics
Kahn AM, Blenman KRM, Sonis ST, Lustberg MB. Strategies to mitigate the toxicity of cancer therapeutics. Advances In Cancer Research 2022, 155: 215-244. PMID: 35779875, DOI: 10.1016/bs.acr.2022.02.006.Peer-Reviewed Original ResearchConceptsAromatase inhibitor-induced musculoskeletal symptomsChemotherapy-induced peripheral neuropathyCancer-related cognitive impairmentCancer treatment symptomsOral mucosal toxicityImmune checkpoint inhibitionTyrosine kinase inhibitorsCancer therapeuticsGastrointestinal toxicityMucosal toxicityAdverse eventsHormone therapySystemic therapyTreatment toxicityPeripheral neuropathyCheckpoint inhibitionSymptom managementMusculoskeletal symptomsRenal toxicityTreatment symptomsOcular toxicityTreatment modalitiesTraditional chemotherapyCognitive impairmentMonoclonal antibodiesComprehensive Analysis of Metabolic Isozyme Targets in Cancer
Marczyk M, Gunasekharan V, Casadevall D, Qing T, Foldi J, Sehgal R, Shan NL, Blenman KRM, O'Meara TA, Umlauf S, Surovtseva YV, Muthusamy V, Rinehart J, Perry RJ, Kibbey R, Hatzis C, Pusztai L. Comprehensive Analysis of Metabolic Isozyme Targets in Cancer. Cancer Research 2022, 82: 1698-1711. PMID: 35247885, PMCID: PMC10883296, DOI: 10.1158/0008-5472.can-21-3983.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetAcetyl-CoA carboxylase 1Therapeutic targetCancer typesCell linesBreast cancer viabilityPatient-derived xenograftsNovel metabolic targetsCorresponding cell linesExpression patternsDrug treatmentMatching normal tissuesRelated commentaryTumor growthMalignant transformationSmall molecule inhibitionCancer viabilityCancer Cell Line EncyclopediaNormal tissuesMetabolic vulnerabilitiesCarboxylase 1Anticancer therapyCellular changesCell proliferationMetabolic reprogramming
2021
Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Yaghoobi V, Moutafi M, Aung TN, Pelekanou V, Yaghoubi S, Blenman K, Ibrahim E, Vathiotis IA, Shafi S, Sharma A, O’Meara T, Fernandez AI, Pusztai L, Rimm DL. Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study. Breast Cancer Research 2021, 23: 113. PMID: 34906209, PMCID: PMC8670126, DOI: 10.1186/s13058-021-01493-w.Peer-Reviewed Original ResearchConceptsNegative breast cancerT cellsTumor microenvironmentAA patientsImmune cellsAA tumorsBreast cancerPurposeTriple-negative breast cancerAfrican AmericansTriple-negative breast cancerCase-control studySignificant differencesActivated T cellsImmunologic biomarkersPD-L1Lymphocytic infiltrationLymphoid infiltrationImmune microenvironmentControl cohortTNBC tumorsMyeloid markersQuantitative immunofluorescenceMean expression levelPatientsTNBCKDM5B 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 therapyBlockadeTumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer
Gonzalez-Ericsson PI, Wulfkhule JD, Gallagher RI, Sun X, Axelrod ML, Sheng Q, Luo N, Gomez H, Sanchez V, Sanders M, Pusztai L, Petricoin E, Blenman K, Balko JM, Team I, Leyland-Jones B, Agency C, Chia S, Serpanchy R, Yu C, University E, McMillan S, Mosley R, Nguyen K, Wood E, Zelnak A, University G, Dillis C, Donnelly R, Harrington T, Isaacs C, Kallakury B, Liu M, Lynce F, Oppong B, Pohlmann P, Tousimis E, Warren R, Willey S, Wong J, Zeck J, Center L, Albain K, Bartolotta M, Bova D, Brooks C, Busby B, Czaplicki K, Duan X, Gamez R, Ganesh K, Gaynor E, Godellas C, Grace-Louthen C, Kuritza T, Lo S, Nagamine A, Perez C, Robinson P, Rosi D, Vaince F, Ward K, Hospital I, Choquette K, Edmiston K, Gallimore H, McGovern J, Mokarem K, Pajaniappan M, Rassulova S, Scott K, Sherwood K, Wright J, Clinic A, Anderson K, Gray R, Myers S, Northfelt D, Pockaj B, Roedig J, Wasif N, Clinic R, Arens A, Boughey J, Brandt K, Carroll J, Chen B, Connors A, Degnim A, Farley D, Greenlee S, Haddad T, Hieken T, Hobday T, Jakub J, Liberte L, Liu M, Loprinzi C, Menard L, Moe M, Moynihan T, O'Sullivan C, Olson E, Peethambaram P, Ruddy K, Russell B, Rynearson A, Smith D, Visscher D, Windish A, Institute H, Cox K, Dawson K, Newton O, Ramirez W, University O, Bengtson H, Bucher J, Chui S, Gilbert-Ghormley B, Hampton R, Kemmer K, Kurdyla D, Nauman D, Spear J, Wilson A, Institute S, Beatty D, Dawson P, Ellis E, Fer M, Hanson J, Goetz M, Haddad T, Iriarte D, Kaplan H, Porter B, Rinn K, Thomas H, Thornton S, Tickman R, Varghis N, Birmingham U, Caterinichia V, Santos J, Falkson C, Forero A, Krontiras H, Vaklavas C, Wei S, University of Arizona, Bauland A, Inclan L, Lewallen D, Powell A, Roney C, Schmidt K, Viscusi R, Wright H, University of California S, Blair S, Boles S, Bykowski J, Datnow B, Densley L, Eghtedari M, Genna V, Hasteh F, Helsten T, Kormanik P, Ojeda-Fournier H, Onyeacholem I, Parker B, Podsada K, Schwab R, Wallace A, Yashar C, University of California S, Alvarado M, Au A, Balassanian R, Benz C, Buxton M, Chen Y, Chien J, D'Andrea C, Davis S, Esserman L, Ewing C, Goga A, Hirst G, Hwang M, Hylton N, Joe B, Lyandres J, Kadafour M, Krings G, Melisko M, Moasser M, Munter P, Ngo Z, Park J, Price E, Rugo H, Veer L, Wong J, Yau C, University of Chicago, Abe H, Jaskowiak N, Nanda R, Olopade F, Schacht D, University of Colorado D, Borges V, Colvin T, Diamond J, Elias A, Finlayson C, Fisher C, Hardesty L, Kabos P, Kounalakis N, Mayordomo J, McSpadden T, Murphy C, Rabinovitch R, Sams S, Shagisultanova E, University of Kansas, Baccaray S, Khan Q, University of Minnesota, Beckwith H, Blaes A, Emory T, Haddad T, Hui J, Klein M, Kuehn-Hajder J, Nelson M, Potter D, Tuttle T, Yee D, Zera R, University of Pennsylvania, Bayne L, Bradbury A, Clark A, DeMichele A, Domchek S, Fisher C, Fox K, Frazee D, Lackaye M, Matro J, McDonald E, Rosen M, Shah P, Tchou J, Volpe M, Center U, Alvarez R, Barcenas C, Berry D, Booser D, Brewster A, Brown P, Gonzalez-Angulo A, Ibrahim N, Karuturi M, Koenig K, Moulder S, Murray J, Murthy R, Pusztai L, Saigal B, Symmans W, Tripathy D, Theriault R, Ueno N, Valero V, California U, Brown M, Carranza M, Flores Y, Lang J, Luna A, Perez N, Tripathy D, Watkins K, Center U, Armstrong S, Boyd C, Chen L, Clark V, Frankel A, Euhus D, Froehlich T, Goudreau S, Haley B, Harker-Murray A, Klemow D, Leitch A, Leon R, Li H, Morgan T, Qureshi N, Rao R, Reeves M, Rivers A, Sadeghi N, Seiler S, Staves B, Tagoe V, Thomas G, Tripathy D, Unni N, Weyandt S, Wooldridge R, Zuckerman J, Universty of Washington, Korde L, Griffin M, Butler B, Cundy A, Rubinstein L, Hixson C. Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer. Clinical Cancer Research 2021, 27: 5299-5306. PMID: 34315723, PMCID: PMC8792110, DOI: 10.1158/1078-0432.ccr-21-0607.Peer-Reviewed Original ResearchConceptsStandard neoadjuvant chemotherapyTriple-negative breast cancerNeoadjuvant chemotherapyBreast cancerMHC-IITumor cellsAnti-PD-1/L1 therapyEstrogen receptor-positive breast cancerPhase II/III clinical trialsNeoadjuvant breast cancer settingPathologic complete response rateHER2-negative breast cancerReceptor-positive breast cancerAddition of immunotherapyHLA-DR positivityBreast cancer settingComplete response rateHER2-negative patientsCohort of patientsEarly breast cancerMHC-II expressionPan-cancer biomarkerImmunotherapy benefitL1 therapyMost patientsCheckpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy
Lo YC, Price C, Blenman K, Patil P, Zhang X, Robert ME. Checkpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory Bowel Disease and Predict Response to Colitis Therapy. American Journal Of Clinical Pathology 2021, 156: 214-228. PMID: 33555016, DOI: 10.1093/ajcp/aqaa217.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseCD8/FOXP3 ratioBiopsy specimensCPI patientsPD-1CD68 scoreFOXP3 ratioBowel diseasePD-L1Antibody-treated patientsCheckpoint inhibitor colitisPD-L1 groupInitial biopsy specimensPD-L1 expressionImmune cell reactionsColonic biopsy specimensDrug-specific differencesIBD groupCheckpoint inhibitorsChronicity scoreActivity scoreImmune phenotypeTherapeutic responseColitisShared pathophysiology
2020
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Rozenblit M, Huang R, Danziger N, Hegde P, Alexander B, Ramkissoon S, Blenman K, Ross JS, Rimm DL, Pusztai L. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal For ImmunoTherapy Of Cancer 2020, 8: e001558. PMID: 33239417, PMCID: PMC7689582, DOI: 10.1136/jitc-2020-001558.Peer-Reviewed Original ResearchConceptsPD-L1 positivity ratePD-L1 positivityPD-L1 expressionDifferent metastatic sitesPrimary tumorMetastatic sitesPositivity rateImmune cellsMetastatic lesionsTumor cellsPD-L1 protein expressionTriple-negative breast cancerMore primary tumorsTriple negative breast cancer tumorsPrimary breast lesionsPrimary outcome measureSoft tissueNegative breast cancerLow positivity rateBreast cancer tumorsBone metastasesFoundation MedicineLymph nodesPD-L1Spearman correlation coefficientPD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionISAC Probe Tag Dictionary: Standardized Nomenclature for Detection and Visualization Labels Used in Cytometry and Microscopy Imaging
Blenman K, Spidlen J, Parks DR, Moore W, Treister A, Leif R, Bray C, Goldberg M, Force I, Brinkman R. ISAC Probe Tag Dictionary: Standardized Nomenclature for Detection and Visualization Labels Used in Cytometry and Microscopy Imaging. Cytometry Part A 2020, 99: 103-106. PMID: 32881392, PMCID: PMC8388112, DOI: 10.1002/cyto.a.24224.Peer-Reviewed Original Research
2019
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysis