Featured Publications
Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test
Fernandez A, Gaule P, Rimm D. Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test. Modern Pathology 2023, 36: 100159. PMID: 36925070, PMCID: PMC10502188, DOI: 10.1016/j.modpat.2023.100159.Peer-Reviewed Original ResearchConceptsPD-L1 signalTumor proportion scoreTissue microarray cohortCell lung cancerPrevious clinical diagnosisWhole tissue sectionsCompanion diagnostic testsMultiple cancer typesMicroarray cohortTMA cohortLaboratory-developed testsPD-L1NSCLC casesLung cancerProportion scorePositive stainingAntibody 22C3Immunohistochemistry testsClinical diagnosisExtracellular domainCancer typesDiagnostic testsArchival tissueDomain antigenAntibodies
2024
BCAM (basal cell adhesion molecule) protein expression in different tumor populations
Burela S, He M, Trontzas I, Gavrielatou N, Schalper K, Langermann S, Flies D, Rimm D, Aung T. BCAM (basal cell adhesion molecule) protein expression in different tumor populations. Discover Oncology 2024, 15: 381. PMID: 39207605, PMCID: PMC11362396, DOI: 10.1007/s12672-024-01244-1.Peer-Reviewed Original ResearchPD-L1 expressionBasal cell adhesion moleculePD-L1Quantitative immunofluorescenceAssociated with better OSPD-L1 protein expressionCancer typesBladder urothelial tumorsProtein expressionMultiple immune checkpointsHead and neckMultiple tumor typesEvidence of hypermethylationImmune checkpointsImmunotherapy responseCell adhesion moleculesTumor typesValidation cohortTumor populationCancer patientsTumorPredictive valueAdhesion moleculesNovel biomarkersWidespread expressionQuantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay
Liu M, Vathiotis I, Robbins C, Chan N, Moutafi M, Burela S, Xirou V, Schalper K, Herbst R, Syrigos K, Rimm D. Quantitative Measurement of HER2 Expression in Non–Small Cell Lung Cancer With a High-Sensitivity Assay. Modern Pathology 2024, 37: 100556. PMID: 38964502, PMCID: PMC11416319, DOI: 10.1016/j.modpat.2024.100556.Peer-Reviewed Original ResearchNon-small cell lung cancerCases of non-small cell lung cancerNon-small cell lung cancer casesT-DXdCell lung cancerHER2 expressionBreast cancerRare case of non-small cell lung cancerQuantitative immunofluorescenceAntibody-drug conjugate trastuzumab deruxtecanLung cancerHER2 antibody-drug conjugatesNon-small cell lung cancer patientsDetecting HER2 expressionHER2-targeted therapyMetastatic breast cancerHER2 protein expressionBreast cancer casesHER2 protein levelsAntibody-drug conjugatesProportion of casesTrastuzumab deruxtecanNSCLC casesFrequency of casesImmunohistochemistry scoreHigh-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)
Moutafi M, Bates K, Aung T, Milian R, Xirou V, Vathiotis I, Gavrielatou N, Angelakis A, Schalper K, Salichos L, Rimm D. High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2024, 12: e009039. PMID: 38857914, PMCID: PMC11168162, DOI: 10.1136/jitc-2024-009039.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsProgrammed cell death protein 1Associated with OSCell lung cancerTissue microarray spotsTissue microarrayValidation cohortLung cancerNon-small cell lung cancer treated with immune checkpoint inhibitorsAssociated with resistance to immunotherapyCell death protein 1Resistance to immunotherapyAssociated with PFSProgression-free survivalSecreted frizzled-related protein 2Cox proportional-hazards model analysisCheckpoint inhibitorsImmunotherapy strategiesTumor compartmentsRetrospective cohortDiscovery cohortLong-term benefitsPatientsCD68Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.
Aung T, Warrell J, Martinez-Morilla S, Gavrielatou N, Vathiotis I, Yaghoobi V, Kluger H, Gerstein M, Rimm D. Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma. Clinical Cancer Research 2024, 30: 3520-3532. PMID: 38837895, PMCID: PMC11326985, DOI: 10.1158/1078-0432.ccr-23-3932.Peer-Reviewed Original ResearchGene signatureResistance to immunotherapyResponse to immunotherapyPrediction of treatment outcomeResistant to treatmentAccurate prediction of treatment outcomePredictive of responseImmunotherapy outcomesMelanoma patientsMelanoma specimensValidation cohortPatient stratificationDiscovery cohortTreatment outcomesImmunotherapyMelanomaTumorPatientsCohortS100BOutcomesGene expression dataGenesCD68+macrophagesExpression dataSACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer.
Garrido-Castro A, Kim S, Desrosiers J, Nanda R, Carey L, Clark A, Sacks R, O'Connor T, Sinclair N, Lo K, Thomas A, Wrabel E, O'Meara T, Lin N, Burstein H, He M, Rimm D, Mittendorf E, Tayob N, Tolaney S. SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. Journal Of Clinical Oncology 2024, 42: lba1004-lba1004. DOI: 10.1200/jco.2024.42.17_suppl.lba1004.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerHR+/HER2- metastatic breast cancerPD-L1 expressionSacituzumab govitecanAntibody drug conjugatesOverall survivalArm BPD-L1Arm ASN-38Study therapyBreast cancerHormone receptor-positive/HER2-negative breast cancerOpen-label phase 2 studyFollow-upDeplete regulatory T cellsFrequent treatment-related toxicitiesHormone receptor-positive/HER2-negativeImproving progression-free survivalTopoisomerase I inhibitor payloadMedian progression-free survivalRandomized phase II trialUpregulated MHC class IT cell effector functionCorrelation of eTILs with recurrence free survival (RFS) in stage IIB-IIIA melanoma and use as biomarker for stratification for clinical trials.
Aung T, Zhang C, Espinoza G, Leung L, Moon J, Horst B, Ferringer T, Nastiuk K, Rimm D, Saenger Y. Correlation of eTILs with recurrence free survival (RFS) in stage IIB-IIIA melanoma and use as biomarker for stratification for clinical trials. Journal Of Clinical Oncology 2024, 42: 9567-9567. DOI: 10.1200/jco.2024.42.16_suppl.9567.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesRecurrence free survivalAmerican Joint Committee on CancerFree survivalInfiltrating lymphocytesRetrospective cohortClinical trialsQuantify tumor-infiltrating lymphocytesStage II-III melanomaTumor-infiltrating lymphocytes groupDiagnostic slidesIIb-IIIaRoswell Park Comprehensive Cancer CenterEarly-stage melanoma patientsCox modelStage IIB-IIICAdjuvant clinical trialsKaplan-Meier curvesMultivariate Cox modelUnivariate Cox modelCox proportional hazards modelsClinical pathological featuresGeisinger Medical CenterProportional hazards modelClinical trial designAn algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers
Xirou V, Moutafi M, Bai Y, Nwe Aung T, Burela S, Liu M, Kimple R, Shabbir Ahmed F, Schultz B, Flieder D, Connolly D, Psyrri A, Burtness B, Rimm D. An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers. Oral Oncology 2024, 152: 106750. PMID: 38547779, PMCID: PMC11060915, DOI: 10.1016/j.oraloncology.2024.106750.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesHead and neck cancerTILs evaluationHPV-positiveNeck cancerPrognostic valueHead and neck squamous cell cancer casesTIL variablesAssociated with favorable prognosisHPV-negative headHPV-negative populationHematoxylin-eosin-stained sectionsCox regression analysisPotential clinical implicationsInter-observer variabilityInfiltrating lymphocytesClinicopathological factorsFavorable prognosisValidation cohortTumor cellsCancer casesProspective settingQuPath softwareRetrospective collectionPredictive significanceDigital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumorsHigh-Plex Assessment of Biomarkers in Tumors
Aung T, Bates K, Rimm D. High-Plex Assessment of Biomarkers in Tumors. Modern Pathology 2024, 37: 100425. PMID: 38219953, DOI: 10.1016/j.modpat.2024.100425.Peer-Reviewed Original Research
2023
B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma
Gavrielatou N, Fortis E, Spathis A, Anastasiou M, Economopoulou P, Foukas G, Lelegiannis I, Rusakiewicz S, Vathiotis I, Aung T, Tissot S, Kastrinou A, Kotsantis I, Vagia E, Panayiotides I, Rimm D, Coukos G, Homicsko K, Foukas P, Psyrri A. B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma. Annals Of Oncology 2023, 35: 340-350. PMID: 38159908, DOI: 10.1016/j.annonc.2023.12.011.Peer-Reviewed Original ResearchProlonged progression-free survivalTertiary lymphoid structuresPD-L1 expressionB cellsM HNSCCCell death protein 1 inhibitionPD-1-based immunotherapyNeck squamous cell cancerNeck squamous cell carcinomaHigher B cell countsIncreased B cellsB cell infiltrationB-cell countsPD-L1 positivityProgression-free survivalTreatment of recurrentSquamous cell cancerBlood immune cell compositionSquamous cell carcinomaBiomarkers of responseImmune cell compositionB-cell-associated genesProtein 1 inhibitionCell death proteinMetastatic headCorrelation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer
Li X, Lee J, Gao Y, Zhang J, Bates K, Rimm D, Zhang H, Smith G, Lawson D, Meisel J, Chang J, Huo L. Correlation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer. Modern Pathology 2023, 37: 100408. PMID: 38135153, DOI: 10.1016/j.modpat.2023.100408.Peer-Reviewed Original ResearchHER2 protein levelsHER2-low breast cancerT-DXdBreast cancerRNA levelsProtein levelsHER2 expressionEarly-stage breast cancerIHC H-scoresTrastuzumab deruxtecanTissue microarray coresClinical trialsMetastatic biopsiesImmunohistochemical assaysH-scoreDrug AdministrationResponse rateUS FoodPatientsIHC assaysCancerRNAscopeRegression analysisCell linesImmunofluorescence scoresEmerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
Lozar T, Wang W, Gavrielatou N, Christensen L, Lambert P, Harari P, Rimm D, Burtness B, Kuhar C, Carchman E. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review. Viruses 2023, 15: 2320. PMID: 38140561, PMCID: PMC10748233, DOI: 10.3390/v15122320.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTriple-negative breast cancerCancer typesPredictive significancePrognostic factorsClinical outcomesPrognostic significanceCell carcinomaHuman cancersCervical squamous cell carcinomaNeck squamous cell carcinomaAvailable clinical evidenceCochrane Central RegisterInferior clinical outcomesPositive prognostic factorNegative predictive factorNegative prognostic factorWeb of ScienceCentral RegisterControlled TrialsCervical cancerClinical evidencePredictive factorsPancreatic cancerEligible studiesMA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC
Gettinger S, Goldberg S, Chiang A, Wilson F, Kim S, Rowen E, Gerrish H, Duffield E, Davies M, Dest V, Jackson R, Pope J, Myint H, Langermann S, Cheng W, Rimm D, Chen L, Herbst R. MA15.07 NC318, an Anti-Siglec-15 Humanized mAb, Alone and in Combination with Pembrolizumab in Immunotherapy Pretreated NSCLC. Journal Of Thoracic Oncology 2023, 18: s155. DOI: 10.1016/j.jtho.2023.09.224.Peer-Reviewed Original ResearchStress Keratin 17 Is a Predictive Biomarker Inversely Associated with Response to Immune Check-Point Blockade in Head and Neck Squamous Cell Carcinomas and Beyond
Lozar T, Laklouk I, Golfinos A, Gavrielatou N, Xu J, Flynn C, Keske A, Yu M, Bruce J, Wang W, Kuhar C, Bailey H, Harari P, Dinh H, Rimm D, Hu R, Lambert P, Fitzpatrick M. Stress Keratin 17 Is a Predictive Biomarker Inversely Associated with Response to Immune Check-Point Blockade in Head and Neck Squamous Cell Carcinomas and Beyond. Cancers 2023, 15: 4905. PMID: 37835599, PMCID: PMC10571921, DOI: 10.3390/cancers15194905.Peer-Reviewed Original ResearchImmune check-point blockadeNeck squamous cell carcinomaCheck-point blockadeSquamous cell carcinomaCK17 expressionDisease controlHNSCC patientsCell carcinomaPredictive biomarkersResponse rateKeratin 17Pembrolizumab-based therapyPembrolizumab-treated patientsPD-L1 expressionProgression-free survivalRNA expressionIndependent retrospective cohortsIndependent validation cohortDecreased response rateLow response rateREMARK criteriaOverall survivalProgressive diseaseRetrospective cohortCXCL10 chemokinesDigital 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 expressionAutomated scoring of tumor-infiltrating lymphocytes informs risk of death from thin melanoma: A nested case-case study
Tan S, Aung T, Claeson M, Acs B, Zhou C, Brown S, Lambie D, Baade P, Pandeya N, Soyer H, Smithers B, Whiteman D, Rimm D, Khosrotehrani K. Automated scoring of tumor-infiltrating lymphocytes informs risk of death from thin melanoma: A nested case-case study. Journal Of The American Academy Of Dermatology 2023, 90: 179-182. PMID: 37730017, DOI: 10.1016/j.jaad.2023.09.026.Peer-Reviewed Original ResearchClassification of Breast Cancer According to ERBB2 Immunohistochemistry Scores
Robbins C, Fernandez A, Rimm D. Classification of Breast Cancer According to ERBB2 Immunohistochemistry Scores. JAMA Oncology 2023, 9: 1298-1299. PMID: 37498606, DOI: 10.1001/jamaoncol.2023.2635.Commentaries, Editorials and LettersImmune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samplesMammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitors