2025
Spatial multi-omics profiling of breast cancer oligo-recurrent lung metastasis
Gao Y, Li B, Jin Y, Cheng J, Tian W, Ying L, Hong L, Xin S, Lin B, Liu C, Sun X, Zhang J, Zhang H, Xie J, Deng X, Dai X, Liu L, Zheng Y, Zhao P, Yu G, Fang W, Bao X. Spatial multi-omics profiling of breast cancer oligo-recurrent lung metastasis. Oncogene 2025, 44: 2268-2282. PMID: 40234722, DOI: 10.1038/s41388-025-03388-y.Peer-Reviewed Original ResearchConceptsLung metastasesTumor microenvironmentBreast cancerImaging Mass CytometryHLA-DR+Primary BCTME componentsEndothelial cellsTumour microenvironment of BCEpithelial cellsPaired lung metastasesExhausted T cellsTriple-negative subtypeMultiplex immunofluorescence analysisPrimary breast cancerAnti-angiogenic therapyDevelopment of therapeutic optionsFormalin-fixed paraffin-embedded (FFPEParaffin-embedded (FFPELung-specific metastasisOligo-metastasisMetastatic tumorsSurgical specimensMultiplex immunofluorescenceT cellsMachine 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, PMCID: PMC11889191, 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 immunofluorescenceAssociation of localized high-risk prostate cancer (PC) and an androgen receptor low subpopulation susceptible to HER2 inhibition.
Sowalsky A, Wilkinson S, Ku A, Lis R, King I, Low D, Trostel S, Baj A, Kartal S, Heyward K, Vo B, Jansen C, Ye H, Harmon S, Kissick H, Pinto P, Choyke P, Turkbey B, Dahut W, Karzai F. Association of localized high-risk prostate cancer (PC) and an androgen receptor low subpopulation susceptible to HER2 inhibition. Journal Of Clinical Oncology 2025, 43: 401-401. DOI: 10.1200/jco.2025.43.5_suppl.401.Peer-Reviewed Original ResearchAndrogen deprivation therapyPathological responseHER2 activationRadical prostatectomyAR activityProstate tumorsHER2 inhibitionProstate cancerMultiplex immunofluorescenceAndrogen receptorMonths prior to radical prostatectomyLocalized high-risk prostate cancerHigh-risk prostate cancerInitiation of neoadjuvant therapyNeoadjuvant androgen deprivation therapyHER2 inhibitorsFlow cytometryTreated with low dosesAssociated with poor outcomesHigh-risk PCIntensive hormone therapyOccult micrometastatic diseasePoor pathologic responseResidual cancer volumeHuman prostate tumors
2024
Spatial Multiomics Profiling of Angioimmunoblastic T-Cell Lymphoma
Enninful A, Foss F, Fan R, Xu M. Spatial Multiomics Profiling of Angioimmunoblastic T-Cell Lymphoma. Blood 2024, 144: 1585-1585. DOI: 10.1182/blood-2024-211129.Peer-Reviewed Original ResearchAngioimmunoblastic T-cell lymphomaT Follicular Helper CellsT-cell lymphomaFollicular dendritic cellsHigh endothelial venulesT cellsTumor cellsTumor microenvironmentB cellsImmune surveillanceMultiplex immunofluorescenceCD21+ follicular dendritic cellsTumor evasion of immune surveillanceNon-neoplastic T cellsEvasion of immune surveillanceEBV-positive B cellsGene activity scoreTissue blocksActivity of tumor cellsReactive B cellsExpression of LMP1Positive B cellsComplex tumor microenvironmentT cell zonesLymph node samplingThe neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1
Romero R, Chu T, González Robles T, Smith P, Xie Y, Kaur H, Yoder S, Zhao H, Mao C, Kang W, Pulina M, Lawrence K, Gopalan A, Zaidi S, Yoo K, Choi J, Fan N, Gerstner O, Karthaus W, DeStanchina E, Ruggles K, Westcott P, Chaligné R, Pe’er D, Sawyers C. The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1. Nature Cancer 2024, 5: 1641-1659. PMID: 39394434, PMCID: PMC11584404, DOI: 10.1038/s43018-024-00838-6.Peer-Reviewed Original ResearchConceptsNeuroendocrine prostate cancerProstate cancerLineage plasticityAndrogen receptor signaling inhibitorsCancer progressionMouse prostate organoidsProstate cancer progressionRB1 deletionProstate organoidsMultiplex immunofluorescenceIn vivo platformTransient regressionDriver mutationsLuminal cellsSignaling InhibitorsAscl1Neuroendocrine transitionLineage transformationOrganoid culturesCancerTherapy outcomeProstateAdenocarcinomaTherapy timeIn vivo microenvironmentBSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE
Kandigian S, Chande S, Dolezal D, Tang T, Wang D, Arnal-Estapé A, Cheok S, McGuone D, Liu Y, Goldberg S, Blondin N, Chiang V, Nguyen D. BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE. Neuro-Oncology Advances 2024, 6: i7-i7. PMCID: PMC11296776, DOI: 10.1093/noajnl/vdae090.020.Peer-Reviewed Original ResearchNon-small cell lung cancerLeptomeningeal diseaseCentral nervous systemLeptomeningeal metastasesParenchymal metastasesCerebrospinal fluidTumor cellsTyrosine kinase inhibitor treatmentCell lung cancerKinase inhibitor treatmentCerebrospinal fluid of patientsCell linesCerebral lateral ventriclesIntra-arterial injectionTGF-b signalingIn vivo passageIntraparenchymal diseaseMechanisms of progressionTumor microenvironmentMultiplex immunofluorescenceAggressive treatmentLeptomeningeal infiltrationPerivascular invasionIntraparenchymal metastasesMurine modelIntratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial.
Matar S, Jegede O, Denize T, Ghandour F, Nabil Laimon Y, El Ahmar N, Bagheri Sheshdeh A, Savla V, Mohanna R, Catalano P, Braun D, Sun M, Gupta S, Vemula S, Freeman G, Motzer R, Atkins M, McDermott D, CHOUEIRI T, Signoretti S. Intratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial. Journal Of Clinical Oncology 2024, 42: 4536-4536. DOI: 10.1200/jco.2024.42.16_suppl.4536.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalMultiplex immunofluorescenceClinical trialsClinical outcomesMetastatic clear cell renal cell carcinomaIntratumoral T cell infiltrationTreated with nivolumab monotherapyMetastatic clear cell RCCClear cell renal cell carcinomaResponse to nivolumabT cell infiltrationCell renal cell carcinomaPoor-risk patientsRenal cell carcinomaClear cell RCCFormalin Fixed ParaffinContinuous variablesNivolumab monotherapyCox proportional hazardsAntigen-experiencedCell RCCCell carcinomaLogistic regression modelsPositive associationMulti-omics analysis reveals immune features associated with immunotherapy benefit in squamous cell lung cancer patients from Phase III Lung-MAP S1400I trial
Parra E, Zhang J, Duose D, Gonzalez-Kozlova E, Redman M, Chen H, Manyam G, Kumar G, Zhang J, Song X, Lazcano R, Marques-Piubelli M, Laberiano-Fernandez C, Rojas F, Zhang B, Taing L, Jhaveri A, Geisberg J, Altreuter J, Michor F, Provencher J, Yu J, Cerami E, Moravec R, Kannan K, Luthra R, Alatrash G, Huang H, Xie H, Patel M, Nie K, Harris J, Argueta K, Lindsay J, Biswas R, Van Nostrand S, Kim-Schulze S, Gray J, Herbst R, Wistuba I, Gettinger S, Kelly K, Bazhenova L, Gnjatic S, Lee J, Zhang J, Haymaker C. Multi-omics analysis reveals immune features associated with immunotherapy benefit in squamous cell lung cancer patients from Phase III Lung-MAP S1400I trial. Clinical Cancer Research 2024, 30: 1655-1668. PMID: 38277235, PMCID: PMC11016892, DOI: 10.1158/1078-0432.ccr-23-0251.Peer-Reviewed Original ResearchConceptsChromosome copy-number variationsOverall survivalMultiplex immunofluorescenceMulti-omics analysisAssociated with superior progression-free survivalNCounter PanCancer Immune Profiling PanelSquamous cell lung cancer patientsSuperior progression-free survivalTreated with nivolumab monotherapyAssociated with worse overall survivalNon-small cell carcinomaAssociated with worse survivalCell lung cancer patientsCold immune microenvironmentProgression-free survivalImmune Profiling PanelRegulatory T cellsPhase III trialsResponse to ICIImmune cell infiltrationHigher immune scoresImmune cell densityLung cancer patientsWhole-exome sequencingImmune gene expression profiles
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 expressionUnique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis
Li X, Li Y, Xiao J, Wang H, Guo Y, Mao X, Shi P, Hou Y, Zhang X, Zhao N, Zheng M, He Y, Ding J, Tan Y, Liao M, Li L, Peng Y, Li X, Pan Q, Xie Q, Li Q, Li J, Li Y, Chen Z, Huang Y, Assis D, Cai S, Boyer J, Huang X, Tang C, Liu X, Peng S, Chai J. Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nature Communications 2023, 14: 29. PMID: 36759512, PMCID: PMC9911648, DOI: 10.1038/s41467-022-34606-w.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisPrimary biliary cholangitis patientsBiliary cholangitisEtiology of primary biliary cholangitisScRNA-seqPathogenic targetsSeverity of diseaseSingle-cell RNA sequencingAMA-M2PBC patientsAutoantibody levelsPolymeric immunoglobulin receptorMemory BMultiplex immunofluorescenceCholangiocyte injuryPlasma cellsAutoimmune diseasesRNAscope analysisCholangiocytesImmunoglobulin receptorBile formationPatientsTherapeutic interventionsMultiplexed IFRNA sequencing
2021
SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation
Redin E, Garmendia I, Lozano T, Serrano D, Senent Y, Redrado M, Villalba M, De Andrea CE, Exposito F, Ajona D, Ortiz-Espinosa S, Remirez A, Bertolo C, Sainz C, Garcia-Pedrero J, Pio R, Lasarte J, Agorreta J, Montuenga LM, Calvo A. SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation. Journal For ImmunoTherapy Of Cancer 2021, 9: e001496. PMID: 33658304, PMCID: PMC7931761, DOI: 10.1136/jitc-2020-001496.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDasatinibDrug Resistance, NeoplasmFemaleHumansImmune Checkpoint InhibitorsLung NeoplasmsLymphocytes, Tumor-InfiltratingMiceMice, 129 StrainPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins c-yesSignal TransductionT-Lymphocytes, RegulatoryTumor MicroenvironmentConceptsNon-small cell lung cancerNumber of TregsMultiplex immunofluorescenceAntiprogrammed cell death 1 (PD-1) antibodySrc family kinase (SFK) inhibitor dasatinibTumor growthInhibitor dasatinibCell death 1 antibodyYES1 expressionDeath-1 antibodyImmune cytotoxic activityPD-1 treatmentPD-1/Treg cell conversionUse of dasatinibVivo depletion experimentsAntitumor activityImmune checkpoint inhibitorsOutcomes of patientsProtein expressionCohort of patientsManagement of patientsCell lung cancerRelevant mouse modelVivo drug testing
2017
Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathways
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