2025
Biological 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
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 benefitsPatientsCD68
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 expressionDeep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer
Barrera C, Corredor G, Viswanathan V, Ding R, Toro P, Fu P, Buzzy C, Lu C, Velu P, Zens P, Berezowska S, Belete M, Balli D, Chang H, Baxi V, Syrigos K, Rimm D, Velcheti V, Schalper K, Romero E, Madabhushi A. Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer. Npj Precision Oncology 2023, 7: 52. PMID: 37264091, PMCID: PMC10235089, DOI: 10.1038/s41698-023-00403-x.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-infiltrating lymphocytesLung cancerEffective adaptive immune responseImmune checkpoint blockersCell lung cancerLung cancer patientsTumor immune microenvironmentAdaptive immune responsesImmune-related biomarkersTreatment-specific outcomesCheckMate 057Histology variantsImmunotherapy resistanceCheckpoint blockersRegulatory cellsTumor rejectionTumor-immune interactionsClinical outcomesImmunosuppressive signalsClinical benefitInfluence prognosisImmune microenvironmentCancer patientsPatient outcomes
2022
P2.12-01 Intratumoral Conventional Type 1 Dendritic Cells (cDC1s) Predict Response to Immunotherapy in Human Non-small Cell Lung Cancer cancer (NSCLC)
Porciuncula A, Henick B, Gianino N, Zugazagoitia J, Vathiotis I, Gavrielatou N, Zacharek S, Rimm D, Schalper K. P2.12-01 Intratumoral Conventional Type 1 Dendritic Cells (cDC1s) Predict Response to Immunotherapy in Human Non-small Cell Lung Cancer cancer (NSCLC). Journal Of Thoracic Oncology 2022, 17: s150. DOI: 10.1016/j.jtho.2022.07.249.Peer-Reviewed Original Research
2021
240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling
Moutafi M, Martinez-Morilla S, Divakar P, Vathiotis I, Gavrielatou N, Aung T, Yaghoobi V, Fernandez A, Fraile J, Schalper K, Rimm D. 240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling. 2021, a258-a258. DOI: 10.1136/jitc-2021-sitc2021.240.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPre-treatment samplesQuantitative immunofluorescencePredictive biomarkersLung cancerHigh PD-L1 expressionExpression of CD66bInitial biomarker discoveryOperable NSCLC patientsStromal immune cellsTwo-sided significance levelPD-L1 expressionImmune checkpoint blockadeRole of neutrophilsCell lung cancerPotential predictive biomarkersGood predictive valueDigital spatial profilingDigital Spatial ProfilerCohort validationICI therapyCheckpoint inhibitorsCheckpoint blockadeNSCLC cohortNSCLC patients
2020
Compactness measures of tumor infiltrating lymphocytes in lung adenocarcinoma are associated with overall patient survival and immune scores
Ding R, Prasanna P, Corredor G, Lu C, Velu P, Le K, Leo P, Beig N, Velcheti V, Rimm D, Schalper K, Madabhushi A. Compactness measures of tumor infiltrating lymphocytes in lung adenocarcinoma are associated with overall patient survival and immune scores. 2020, 2. DOI: 10.1117/12.2549588.Peer-Reviewed Original Research
2019
MA15.05 Computerized Measurements of Cellular Diversity on H&E Tissue Are Prognostic of OS and Associated with Mutational Status in NSCLC
Velcheti V, Lu C, Bera K, Wang X, Fu P, Yang M, Rimm D, Schalper K, Madabhushi A. MA15.05 Computerized Measurements of Cellular Diversity on H&E Tissue Are Prognostic of OS and Associated with Mutational Status in NSCLC. Journal Of Thoracic Oncology 2019, 14: s310. DOI: 10.1016/j.jtho.2019.08.622.Peer-Reviewed Original ResearchMA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer
Wang X, Barrera C, Bera K, Lu C, Feldman M, Schalper K, Rimm D, Velcheti V, Madabhushi A. MA25.02 Arrangement and Architecture of Tumor-Infiltrating Lymphocyte on H&E Slides Predict OS in Nivolumab Treated Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: s350-s351. DOI: 10.1016/j.jtho.2019.08.710.Peer-Reviewed Original ResearchPhenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer
Barrera C, Corredor G, Wang X, Schalper K, Rimm D, Velcheti V, Madabhushi A, Castro E. Phenotyping tumor infiltrating lymphocytes (PhenoTIL) on H&E tissue images: predicting recurrence in lung cancer. Progress In Biomedical Optics And Imaging 2019, 10956: 1095607-1095607-8. DOI: 10.1117/12.2513048.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesTIL densityLung cancerEarly stage non-small cell lung cancer patientsNon-small cell lung cancer patientsCell lung cancer patientsEarly-stage lung cancerKaplan-Meier analysisLung cancer patientsStage lung cancerLikelihood of recurrenceBetter prognosisLate recurrenceCancer patientsDifferent cancer typesDisease outcomeRecurrenceDifferent subtypesCancer typesLymphocytesCancerPatientsPrognosisIndependent validation
2018
Tumor PD-L1 heterogeneity in non-small cell lung cancer: Does biopsy size and volume matter?
Khunger M, Bordeaux J, Dakappagari N, Vaupel C, Khunger A, Hu B, Schalper K, Rimm D, Velcheti V. Tumor PD-L1 heterogeneity in non-small cell lung cancer: Does biopsy size and volume matter? Journal Of Clinical Oncology 2018, 36: 12058-12058. DOI: 10.1200/jco.2018.36.15_suppl.12058.Peer-Reviewed Original ResearchPD-1/PD-L1 interaction and CD25/FOXP3+ t cells to predict survival benefit from adjuvant chemotherapy in early stage non–small-cell lung cancer (ES-NSCLC).
Bordeaux J, Dakappagari N, Pennell N, Stevenson J, Khunger M, Vaupel C, Schalper K, Rimm D, Velcheti V. PD-1/PD-L1 interaction and CD25/FOXP3+ t cells to predict survival benefit from adjuvant chemotherapy in early stage non–small-cell lung cancer (ES-NSCLC). Journal Of Clinical Oncology 2018, 36: 12059-12059. DOI: 10.1200/jco.2018.36.15_suppl.12059.Peer-Reviewed Original ResearchExpression and clinical significance of antigen presentation components beta-2 microglobulin, HLA class I heavy chains, and HLA class II in non-small cell lung cancer (NSCLC).
Datar I, Villarroel-Espindola F, Henick B, Syrigos K, Toki M, Rimm D, Ferrone S, Herbst R, Schalper K. Expression and clinical significance of antigen presentation components beta-2 microglobulin, HLA class I heavy chains, and HLA class II in non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2018, 36: 12015-12015. DOI: 10.1200/jco.2018.36.15_suppl.12015.Peer-Reviewed Original ResearchMultiplexed analysis of myeloid cell (MC) markers to characterize the innate immune composition and clinical features of human non-small cell lung carcinomas (NSCLC).
Henick B, Datar I, Villarroel-Espindola F, Sanmamed M, Yu J, Tuktamyshov R, Li A, Toki M, Syrigos K, Rimm D, Chen L, Herbst R, Schalper K. Multiplexed analysis of myeloid cell (MC) markers to characterize the innate immune composition and clinical features of human non-small cell lung carcinomas (NSCLC). Journal Of Clinical Oncology 2018, 36: 12002-12002. DOI: 10.1200/jco.2018.36.15_suppl.12002.Peer-Reviewed Original ResearchClinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer
Gettinger SN, Wurtz A, Goldberg SB, Rimm D, Schalper K, Kaech S, Kavathas P, Chiang A, Lilenbaum R, Zelterman D, Politi K, Herbst R. Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2018, 13: 831-839. PMID: 29578107, PMCID: PMC6485248, DOI: 10.1016/j.jtho.2018.03.008.Peer-Reviewed Original ResearchConceptsPD-1 axis inhibitorsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerInhibitor therapyLocal therapyLymph nodesLung cancerSurvival rateSolid Tumors v1.1Response Evaluation CriteriaSite of diseaseProgression of diseaseProgressive diseaseClinical patternLN metastasisSuch patientsClinical featuresMedian timeRadiographic featuresTumor regressionProlonged benefitPatientsTherapyResponse criteria
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutationsMA 13.03 Quantitative Spatial Profiling of PD-1/PD-L1 Interaction Predicts Response to Adjuvant Chemotherapy Non–Small-Cell Lung Cancer
Velcheti V, Bordeaux J, Dakappagari N, Pennell N, Stevenson J, Khunger M, Kim J, Schalper K, Rimm D. MA 13.03 Quantitative Spatial Profiling of PD-1/PD-L1 Interaction Predicts Response to Adjuvant Chemotherapy Non–Small-Cell Lung Cancer. Journal Of Thoracic Oncology 2017, 12: s1852. DOI: 10.1016/j.jtho.2017.09.562.Peer-Reviewed Original Research
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