2024
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.
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 function
2023
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
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 chemokinesDeep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases
Chatziioannou E, Roßner J, Aung T, Rimm D, Niessner H, Keim U, Serna-Higuita L, Bonzheim I, Cuellar L, Westphal D, Steininger J, Meier F, Pop O, Forchhammer S, Flatz L, Eigentler T, Garbe C, Röcken M, Amaral T, Sinnberg T. Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases. EBioMedicine 2023, 93: 104644. PMID: 37295047, PMCID: PMC10363450, DOI: 10.1016/j.ebiom.2023.104644.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesMultiple Cox regressionMelanoma-specific survivalCox regressionTumor thicknessCutaneous melanomaPrimary melanomaAssessment of TILsPD-1 checkpoint inhibitionSignificant unfavourable prognostic factorLonger progression-free survivalDistant metastasis-free survivalSimple Cox regressionUnfavourable survival outcomeFirst-line therapyProgression-free survivalUnfavourable prognostic factorCutaneous melanoma patientsMetastasis-free survivalPresence of ulcerationPrimary cutaneous melanomaCox regression modelPrimary melanoma samplesPrimary tissuesOverall survivalSubsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patternsDigital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survivalSpatial characterization and quantification of CD40 expression across cancer types
Bates K, Vathiotis I, MacNeil T, Ahmed F, Aung T, Katlinskaya Y, Bhattacharya S, Psyrri A, Yea S, Parkes A, Sadraei N, Roychoudhury S, Rimm D, Gavrielatou N. Spatial characterization and quantification of CD40 expression across cancer types. BMC Cancer 2023, 23: 220. PMID: 36894898, PMCID: PMC9996913, DOI: 10.1186/s12885-023-10650-7.Peer-Reviewed Original ResearchConceptsCD40 expressionSolid tumorsTumor cellsQuantitative immunofluorescencePatient cohortPancreatic cancerCancer typesExpression of CD40Large patient cohortOvarian cancer populationTissue microarray formatDifferent solid tumorsInnate immune responseTNF receptor family membersAvailable patient cohortNSCLC populationOverall survivalPrognostic impactReceptor family membersCancer populationAdenocarcinoma populationImmune cellsOvarian cancerPancreatic adenocarcinomaPositivity rate
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityDigital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma.
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Psyrri A, Rimm D. Digital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2022, 40: 6050-6050. DOI: 10.1200/jco.2022.40.16_suppl.6050.Peer-Reviewed Original ResearchNeck squamous cell carcinomaM HNSCC patientsSquamous cell carcinomaB2M expressionOverall survivalHNSCC patientsValidation cohortCell carcinomaB2MPre-treatment biopsy samplesUnivariate Cox regression modelM expressionFunctional antigen presentationHigh beta2-microglobulinTreatment of recurrentImmune checkpoint expressionCox regression modelImmune cell markersStandard of careIndependent validation cohortSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyImmune stromaM HNSCCClinical 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 D, 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. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.16_suppl.516.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerMultivariate logistic regression analysisPD-L1 statusLogistic regression analysisAA raceOverall survivalPathologic responseClinical trialsBreast cancerEarly-stage triple-negative breast cancerIncidence of irAEsPhase I/II trialPathologic complete response rateSignificant associationPhase I/II clinical trialsBaseline body mass indexSafety of immunotherapyWeekly nab-paclitaxelCharlson Comorbidity IndexComplete response ratePrimary efficacy endpointPD-L1 expressionBody mass indexBreast cancer recurrenceAssociation of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer
Gavrielatou N, Liu Y, Vathiotis I, Zugazagoitia J, Aung TN, Shafi S, Fernandez A, Schalper K, Psyrri A, Rimm DL. Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer. Clinical Cancer Research 2022, 28: clincanres.2649.2021. PMID: 34686497, PMCID: PMC8776595, DOI: 10.1158/1078-0432.ccr-21-2649.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerBest overall responsePD-L1 tumor proportion scorePD-1/PD-L1Immune checkpoint inhibitorsProgression-free survivalTumor proportion scoreCell lung cancerPD-L1Immunotherapy outcomesCheckpoint inhibitorsOverall survivalQuantitative immunofluorescenceLung cancerProportion scoreAdvanced non-small cell lung cancerLocal T cell responsesCell death protein 1Immunotherapy-treated patientsMultiplexed quantitative immunofluorescencePD-1 expressionPD-L1 expressionDeath protein 1Selection of patientsT cell responses
2021
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer
MacNeil T, Vathiotis IA, Shafi S, Aung TN, Zugazagoitia J, Gruver AM, Driscoll K, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer. Cancers 2021, 13: 5501. PMID: 34771664, PMCID: PMC8583434, DOI: 10.3390/cancers13215501.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesPancreatic ductal adenocarcinomaCancer-associated fibroblastsImmune checkpoint blockadePancreatic cancerCheckpoint blockadePDAC patientsTumor microenvironmentQuantitative immunofluorescenceExpression levelsProgression-free survivalLarge retrospective cohortMajority of patientsPotential prognostic valueLow tumor immunogenicityPotential clinical utilityDesmoplastic tumor microenvironmentImmunoinhibitory proteinOverall survivalRetrospective cohortIndependent predictorsImmunotherapy drugsPrognostic significancePrognostic valueTumor expressionHigh Counts of CD68+ and CD163+ Macrophages in Mantle Cell Lymphoma Are Associated With Inferior Prognosis
Li P, Yuan J, Ahmed FS, McHenry A, Fu K, Yu G, Cheng H, Xu ML, Rimm DL, Pan Z. High Counts of CD68+ and CD163+ Macrophages in Mantle Cell Lymphoma Are Associated With Inferior Prognosis. Frontiers In Oncology 2021, 11: 701492. PMID: 34527580, PMCID: PMC8435777, DOI: 10.3389/fonc.2021.701492.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaPD-L1 expressionMantle cell lymphomaKi67 proliferation rateOverall survivalPD-L1Cell lymphomaImmune checkpoint molecule PD-L1Low PD-L1 expressionLarge B-cell lymphomaX-tile softwareHigher Ki67 proliferation rateLog-rank testMCL casesNumber of M1Tissue microarray blocksB-cell lymphomaProliferation rateImmunophenotypic subclassificationInferior OSLow Ki67Better OSPoor OSPrognostic impactInferior prognosisProgrammed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC
Doroshow DB, Wei W, Gupta S, Zugazagoitia J, Robbins C, Adamson B, Rimm DL. Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC. Journal Of Thoracic Oncology 2021, 16: 2139-2143. PMID: 34455068, PMCID: PMC8612948, DOI: 10.1016/j.jtho.2021.07.032.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreHigh PD-L1 tumor proportion scoreOverall survivalNonsquamous histologySquamous NSCLCNonsquamous NSCLCPredictive biomarkersProportion scoreDeath ligand 1 (PD-L1) tumor proportion scoreElectronic health record-derived databaseFirst-line pembrolizumab therapyPD-1 expression levelsPD-L1 expression levelsCommunity oncology clinicsMedian OS differenceSingle-agent pembrolizumabImmune checkpoint inhibitorsImproved overall survivalMedian overall survivalPrimary end pointFirst-line pembrolizumabFirst-line therapyPD-L1 expressionPD-L1 testingQuantitative Assessment of CD200 and CD200R Expression in Lung Cancer
Vathiotis IA, MacNeil T, Zugazagoitia J, Syrigos KN, Aung TN, Gruver AM, Vaillancourt P, Hughes I, Hinton S, Driscoll K, Rimm DL. Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer. Cancers 2021, 13: 1024. PMID: 33804482, PMCID: PMC7957629, DOI: 10.3390/cancers13051024.Peer-Reviewed Original ResearchLung cancer patientsCD200R expressionClinicopathologic characteristicsPD-L1Cancer patientsLung cancerImmune cellsLarge-cell neuroendocrine carcinoma patientsMutation statusNon-small cell lung cancer patientsCell lung cancer patientsQuantitative immunofluorescenceMultiplexed quantitative immunofluorescenceNeuroendocrine carcinoma patientsExpression of CD200Lung cancer cohortTumor cell stainingLCNEC patientsOverall survivalCarcinoma patientsImmune checkpointsImmune therapyTumor positivitySquamous differentiationCancer cohortSpatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Datar IJ, Hauc SC, Desai S, Gianino N, Henick B, Liu Y, Syrigos K, Rimm DL, Kavathas P, Ferrone S, Schalper KA. Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer. Clinical Cancer Research 2021, 27: 2837-2847. PMID: 33602682, PMCID: PMC8734284, DOI: 10.1158/1078-0432.ccr-20-3655.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerNK cell infiltrationReduced T cellCell lung cancerHLA class IIT cellsLung cancerHLA classClinical significanceSubunit expressionHLA class II downregulationΒ2MClass IIHLA genesHuman leukocyte antigen classShorter overall survivalTumor microenvironment compositionClass II β chainImmune contextureOverall survivalLung malignancyNatural killerPatient survivalCell infiltrationClinicopathologic variables
2020
A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study
Lu C, Bera K, Wang X, Prasanna P, Xu J, Janowczyk A, Beig N, Yang M, Fu P, Lewis J, Choi H, Schmid RA, Berezowska S, Schalper K, Rimm D, Velcheti V, Madabhushi A. A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study. The Lancet Digital Health 2020, 2: e594-e606. PMID: 33163952, PMCID: PMC7646741, DOI: 10.1016/s2589-7500(20)30225-9.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaEarly-stage non-small cell lung carcinomaOverall survivalRetrospective studyEarly-stage non-small cell lung cancerNon-small cell lung cancerMultivariable Cox regression analysisCell differentiation pathwayCox proportional hazards modelLung squamous cell carcinomaEarly-stage LUADOverall survival informationCox regression analysisPrognosis of patientsCell lung cancerRisk stratification modelSquamous cell carcinomaLung cancer pathogenesisIndependent validation cohortCell lung carcinomaProportional hazards modelComputer-extracted featuresAdjuvant therapyDifferentiation pathwayValidation cohortBiomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Zugazagoitia J, Gupta S, Liu Y, Fuhrman K, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling. Clinical Cancer Research 2020, 26: 4360-4368. PMID: 32253229, PMCID: PMC7442721, DOI: 10.1158/1078-0432.ccr-20-0175.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-1 checkpoint blockadeCell lung cancerCheckpoint blockadeLung cancerAdvanced non-small cell lung cancerUnivariate unadjusted analysisProgression-free survivalImmune cell countsMinority of patientsRobust predictive biomarkersBiomarkers of responseLarge independent cohortsSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyOverall survivalClinical outcomesImmune predictorsHigher CD56NSCLC casesPredictive biomarkersUnadjusted analysesImmune parametersTissue microarrayPD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC).
Doroshow D, Wei W, Zugazagoitia J, Robbins C, Gupta S, Adamson B, Rimm D. PD-L1 tumor proportion score and clinical benefit from first-line pembrolizumab in patients with advanced nonsquamous versus squamous non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: 9539-9539. DOI: 10.1200/jco.2020.38.15_suppl.9539.Peer-Reviewed Original ResearchPD-L1 tumor proportion scoreNon-small cell lung cancerTumor proportion scoreMedian overall survivalFirst-line pembrolizumabOverall survivalLonger OSHazard ratioPD-L1Predictive biomarkersNS patientsProportion scoreSquamous non-small cell lung cancerAppropriate predictive biomarkersUnadjusted hazard ratioNSCLC tumor cellsLonger overall survivalCell lung cancerCheckpoint inhibitor useDe-identified databaseHistology interactionNonsquamous cancerSQ patientsSquamous histologyPrimary endpoint
2019
An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma
Acs B, Ahmed FS, Gupta S, Wong P, Gartrell RD, Sarin Pradhan J, Rizk EM, Gould Rothberg BE, Saenger YM, Rimm DL. An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma. Nature Communications 2019, 10: 5440. PMID: 31784511, PMCID: PMC6884485, DOI: 10.1038/s41467-019-13043-2.Peer-Reviewed Original ResearchConceptsOpen sourceOpen source softwareSource softwareTIL scoreTraining setDisease-specific overall survivalHigh TIL scorePoor prognosis cohortsSubset of patientsAlgorithmIndependent prognostic markerBroad adoptionAssessment of tumorOverall survivalFavorable prognosisMelanoma patientsMultivariable analysisValidation cohortIndependent associationPrognostic markerSeparate patientsPrognostic variablesIndependent cohortRetrospective collectionMelanomaQuantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomes