2023
Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy
Martinez-Morilla S, Moutafi M, Fernandez A, Jessel S, Divakar P, Wong P, Garcia-Milian R, Schalper K, Kluger H, Rimm D. Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy. OncoImmunology 2023, 12: 2260618. PMID: 37781235, PMCID: PMC10540659, DOI: 10.1080/2162402x.2023.2260618.Peer-Reviewed Original ResearchConceptsDigital spatial profilingImmune checkpoint inhibitor therapyShorter progression-free survivalQuantitative immunofluorescenceCheckpoint inhibitor therapyProgression-free survivalMetastatic melanoma patientsPre-treatment specimensIndependent validation cohortMetastatic melanoma casesAdjuvant settingNanoString GeoMxMultivariable adjustmentAdverse eventsImmunotherapy cohortInhibitor therapyPD-L1Immune markersMelanoma patientsUnivariable analysisValidation cohortImmune cellsMelanoma casesMultiplex immunofluorescenceCD95 expression
2020
The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice
Gonzalez‐Ericsson P, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, Michiels S, Le Quesne J, Nielsen TO, Lænkholm A, Fox SB, Adam J, Bartlett JM, Rimm DL, Quinn C, Peeters D, Dieci MV, Vincent‐Salomon A, Cree I, Hida AI, Balko JM, Haynes HR, Frahm I, Acosta‐Haab G, Balancin M, Bellolio E, Yang W, Kirtani P, Sugie T, Ehinger A, Castaneda CA, Kok M, McArthur H, Siziopikou K, Badve S, Fineberg S, Gown A, Viale G, Schnitt SJ, Pruneri G, Penault‐Llorca F, Hewitt S, Thompson EA, Allison KH, Symmans WF, Bellizzi AM, Brogi E, Moore DA, Larsimont D, Dillon DA, Lazar A, Lien H, Goetz MP, Broeckx G, Bairi K, Harbeck N, Cimino‐Mathews A, Sotiriou C, Adams S, Liu S, Loibl S, Chen I, Lakhani SR, Juco JW, Denkert C, Blackley EF, Demaria S, Leon‐Ferre R, Gluz O, Zardavas D, Emancipator K, Ely S, Loi S, Salgado R, Sanders M, Group I. The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice. The Journal Of Pathology 2020, 250: 667-684. PMID: 32129476, DOI: 10.1002/path.5406.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesPD-L1Breast cancerPatient selectionInter-reader reproducibilityEarly-stage triple-negative breast cancerPD-1/PD-L1 inhibitorsStage triple-negative breast cancerAdvanced triple-negative breast cancerPD-1/PD-L1High tumor-infiltrating lymphocytesImmune checkpoint inhibitor therapyAddition of atezolizumabPD-L1 assessmentSuboptimal patient selectionCheckpoint inhibitor therapyOptimal patient selectionPD-L1 expressionPD-L1 inhibitorsDaily practiceStandard of careImmuno-therapeutic approachesNegative breast cancerEosin-stained slides
2019
Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma
Gupta S, McCann L, Chan YGY, Lai EW, Wei W, Wong PF, Smithy JW, Weidler J, Rhees B, Bates M, Kluger HM, Rimm DL. Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 254. PMID: 31533832, PMCID: PMC6751819, DOI: 10.1186/s40425-019-0731-9.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFollow-Up StudiesGene Expression ProfilingHumansInterferon Regulatory Factor-1MaleMelanomaMiddle AgedMonitoring, ImmunologicPrognosisProgrammed Cell Death 1 Ligand 2 ProteinProgression-Free SurvivalReal-Time Polymerase Chain ReactionRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSkin NeoplasmsConceptsCompanion diagnostic testsImmunotherapy outcomesMelanoma patientsClinical benefitAnti-PD-1 therapyImmune checkpoint inhibitor therapyMRNA expressionQuantitative immunofluorescenceDiagnostic testsCheckpoint inhibitor therapyReal-time quantitative reverse transcription polymerase chain reactionMetastatic melanoma patientsQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionYale Pathology archivesParaffin-embedded tissue sectionsAdjuvant settingICI therapyOS associationInhibitor therapyBaseline variablesMetastatic melanomaPredictive biomarkersPolymerase chain reaction
2018
Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial
Pelekanou V, Barlow WE, Nahleh Z, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L. Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial. Molecular Cancer Therapeutics 2018, 17: molcanther.1005.2017. PMID: 29588392, PMCID: PMC6548451, DOI: 10.1158/1535-7163.mct-17-1005.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPathologic complete responseTIL countPosttreatment tissuePD-L1Estrogen receptorImmune checkpoint inhibitor therapyPD-L1 positivity rateTumor-infiltrating lymphocyte countsDoxorubicin/cyclophosphamideCheckpoint inhibitor therapyPD-L1 levelsMol Cancer TherNab-paclitaxelLymphocyte countResidual cancerComplete responseER statusImmune changesInhibitor therapyCox regressionPatient populationControl armClinical trialsPositivity rate
2016
Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group
Denkert C, Wienert S, Poterie A, Loibl S, Budczies J, Badve S, Bago-Horvath Z, Bane A, Bedri S, Brock J, Chmielik E, Christgen M, Colpaert C, Demaria S, Van den Eynden G, Floris G, Fox SB, Gao D, Ingold Heppner B, Kim SR, Kos Z, Kreipe HH, Lakhani SR, Penault-Llorca F, Pruneri G, Radosevic-Robin N, Rimm DL, Schnitt SJ, Sinn BV, Sinn P, Sirtaine N, O'Toole SA, Viale G, Van de Vijver K, de Wind R, von Minckwitz G, Klauschen F, Untch M, Fasching PA, Reimer T, Willard-Gallo K, Michiels S, Loi S, Salgado R. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Modern Pathology 2016, 29: 1155-1164. PMID: 27363491, DOI: 10.1038/modpathol.2016.109.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesEvaluation of TILsIntraclass correlation coefficientBreast cancerInternational Immuno-Oncology Biomarker Working GroupImmune checkpoint inhibitor therapyBiomarker Working GroupImmuno-oncology biomarkersDiagnostic practiceKappa valuesInhibitor therapyInternational Working GroupImmunological parametersClinical trialsClinical studiesFleiss kappa valuePrespecified endpointsStudy aimWorking GroupMean concordanceStandardized reportingCancerRing studiesStandardized evaluationDifferent pathologists