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
2025
Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial
Zerdes I, Matikas A, Mezheyeuski A, Manikis G, Acs B, Johansson H, Boyaci C, Boman C, Poncet C, Ignatiadis M, Bai Y, Rimm D, Cameron D, Bonnefoi H, Bergh J, MacGrogan G, Foukakis T. Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial. Npj Breast Cancer 2025, 11: 23. PMID: 40055382, DOI: 10.1038/s41523-025-00730-1.Peer-Reviewed Original ResearchPathological complete responseAssociated with pathologic complete responseBreast cancerTriple-negativeCD8+ T cell expressionImmune infiltrate characterizationPretreatment tumor biopsiesTP53-mutated tumorsTumor immune microenvironmentTumor microenvironment componentsT cell expressionImmune cell subsetsTumors of patientsTumor-host interactionsBreast cancer trialsNeoadjuvant trialsComplete responseTN tumorsCD4+Tumor biopsiesCell subsetsPrognostic correlationPrognostic implicationsImmune infiltrationMultiplex immunofluorescenceQuantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-Type Non-Small Cell Lung Cancer.
Trontzas I, He M, Wurtz A, Robbins C, Robinson N, Bates K, Liu M, Aung T, Scott L, Chan N, Burela S, Schillo J, Liebler D, Hill S, Morrison R, Vathiotis I, Syrigos K, Goldberg S, Politi K, Rimm D. Quantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-Type Non-Small Cell Lung Cancer. Clinical Cancer Research 2025 PMID: 40047548, DOI: 10.1158/1078-0432.ccr-24-3347.Peer-Reviewed Original ResearchNon-small cell lung cancerAntibody-drug conjugatesAntibody-drug conjugate targetsEGFR mutationsCell lung cancerEGFR expressionQuantitative immunofluorescenceWild-type non-small cell lung cancerLung cancerAssociated with EGFR mutationsAssociated with EGFR expressionTissue microarray cohortAssociation of HER2Management of patientsAssay limitProportion of casesMutation statusTROP2 expressionMicroarray cohortEGFRQuantitative protein expressionTreatment sequencePatientsCell linesWild-type127 Analytical Validation and Prospective Study of a High-Sensitivity HER2 (HS-HER2) Quantitative Immunofluorescence Assay for Enhanced Stratification of HER2-Low Breast Cancer Patients
Chan N, Gaule P, Benanto J, Robbins C, Scott L, Hill S, Morrison R, Liebler D, Fulton R, Rimm D. 127 Analytical Validation and Prospective Study of a High-Sensitivity HER2 (HS-HER2) Quantitative Immunofluorescence Assay for Enhanced Stratification of HER2-Low Breast Cancer Patients. Laboratory Investigation 2025, 105: 102351. DOI: 10.1016/j.labinv.2024.102351.Peer-Reviewed Original Research119 Reading vs Measuring: Comparison of Pathologist-Based Scores to Analytic Measurements
Bates K, Fernandez A, Martinez-Morilla S, Chan N, Benanto J, Reisenbichler E, Rimm D. 119 Reading vs Measuring: Comparison of Pathologist-Based Scores to Analytic Measurements. Laboratory Investigation 2025, 105: 102343. DOI: 10.1016/j.labinv.2024.102343.Peer-Reviewed Original ResearchBiological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach
Lopez de Rodas M, Villalba-Esparza M, Sanmamed M, Chen L, Rimm D, Schalper K. Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach. Nature Reviews Clinical Oncology 2025, 22: 163-181. PMID: 39820025, DOI: 10.1038/s41571-024-00984-x.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesImmune-checkpoint inhibitorsTumor-infiltrating lymphocyte subpopulationsClinical significance of tumor-infiltrating lymphocytesPredictive value of tumor-infiltrating lymphocytesSignificance of tumor-infiltrating lymphocytesStudy of tumor-infiltrating lymphocytesImmune-checkpoint inhibitor therapyImmune-mediated tumor eliminationEra of immunotherapyT cell dysfunctionBiomarkers of responseSolid tumor typesImmunotherapeutic approachesAntigen-reactiveTumor microenvironmentTumor typesClinical outcomesTumor eliminationClinical significanceSingle-cell transcriptomicsPredictive valueAnticancer mechanismClinical implicationsResistance mechanismsSociety for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing
Taube J, Sunshine J, Angelo M, Akturk G, Eminizer M, Engle L, Ferreira C, Gnjatic S, Green B, Greenbaum S, Greenwald N, Hedvat C, Hollmann T, Jiménez-Sánchez D, Korski K, Lako A, Parra E, Rebelatto M, Rimm D, Rodig S, Rodriguez-Canales J, Roskes J, Schalper K, Schenck E, Steele K, Surace M, Szalay A, Tetzlaff M, Wistuba I, Yearley J, Bifulco C. Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing. Journal For ImmunoTherapy Of Cancer 2025, 13: e008875. PMID: 39779210, PMCID: PMC11749220, DOI: 10.1136/jitc-2024-008875.Peer-Reviewed Original ResearchConceptsSociety for ImmunotherapyMultiplex immunohistochemistrySociety for Immunotherapy of CancerImmunotherapy of cancerImmune cell subsetsPractice guidelinesCell subsetsTumor microenvironmentGeneration of robust dataTask ForceComplex immunophenotypeAcademic centersMarker expressionMIHC/IFClinical useClinical implementationImmunohistochemistryQuantitative image analysisImmunofluorescenceDiagnostic companiesRobust dataAssayImage analysisManagement considerationsStaining protocol
2024
215P Differential spatial gene expression and clinicopathologic characteristics are associated with exceptional response to immune checkpoint inhibition in recurrent/metastatic head and neck cancer
Gavrielatou N, Spathis A, Anastasiou M, Economopoulou P, Foukas G, Lelegiannis I, Aung T, Kotsantis I, Vagia E, Panayiotides I, Rimm D, Foukas P, Psyrri A. 215P Differential spatial gene expression and clinicopathologic characteristics are associated with exceptional response to immune checkpoint inhibition in recurrent/metastatic head and neck cancer. Immuno-Oncology Technology 2024, 24: 100968. DOI: 10.1016/j.iotech.2024.100968.Peer-Reviewed Original ResearchThe analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably?
Vidal J, Tsiknakis N, Staaf J, Bosch A, Ehinger A, Nimeus E, Salgado R, Bai Y, Rimm D, Hartman J, Acs B. The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably? EClinicalMedicine 2024, 78: 102928. PMID: 39634035, PMCID: PMC11615110, DOI: 10.1016/j.eclinm.2024.102928.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor-infiltrating lymphocytesBreast Cancer Research FoundationPrognostic validityMetastatic triple-negative breast cancerDisease-free survival endpointsHazard ratioHost anti-tumor immunityScored tumor infiltrating lymphocytesTumor-infiltrating lymphocyte scoresTriple-negative breast cancer patientsYears median follow-upTumour-infiltrating lymphocyte assessmentAnti-tumor immunityMedian follow-upIndependent prospective cohortTNBC tumorsPrognostic potentialProspective cohortBreast cancerPrognostic performanceAnalytic cohortFollow-upSchool of MedicineSwedish Society for Medical Research109 Development of a novel immuno-metabolic spatial signature to predict response and resistance to immunotherapy in NSCLC patients
Markovits E, Monkman J, Aung T, Reeves J, O’Byrne K, Czertock R, Puig O, Rimm D, Kulasinghe A. 109 Development of a novel immuno-metabolic spatial signature to predict response and resistance to immunotherapy in NSCLC patients. 2024, a119-a119. DOI: 10.1136/jitc-2024-sitc2024.0109.Peer-Reviewed Original Research127 Digital pathology prognostic biomarkers- time for clinical application in melanoma
Saenger Y, Zhang C, Espinoza G, Bracero Y, Kenchappa D, Moon J, Matteo A, Bioh L, Sultana S, Singh A, Aung T, Gartrell R, Leung L, Ferringer T, Chang R, Horst B, Nastiuk K, Rimm D, Geskin L. 127 Digital pathology prognostic biomarkers- time for clinical application in melanoma. 2024, a140-a141. DOI: 10.1136/jitc-2024-sitc2024.0127.Peer-Reviewed Original ResearchBCAM (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 tumorsImage‐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
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