2024
Quantitative 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, 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 scoreImmune Cell Dynamics in Epidermal Growth Factor Receptor (EGFR) Mutated Non-Small Cell Lung Cancer (NSCLC) Treated with Afatinib and Pembrolizumab: Results from a Phase IB Study
Riess J, Lara M, de Rodas M, Luxardi G, Herbert S, Shimoda M, Kelly K, Meerlev A, Moore E, Beckett L, Monjazeb A, Schalper K, Maverakis E, Gandara D. Immune Cell Dynamics in Epidermal Growth Factor Receptor (EGFR) Mutated Non-Small Cell Lung Cancer (NSCLC) Treated with Afatinib and Pembrolizumab: Results from a Phase IB Study. JTO Clinical And Research Reports 2024, 100706. DOI: 10.1016/j.jtocrr.2024.100706.Peer-Reviewed Original ResearchImmune related adverse eventsNon-small cell lung cancerEGFR-mutant non-small cell lung cancerMaximum tolerated doseEpidermal growth factor receptorImmune cell subsetsT cellsEGFR-TKIsCell subsetsPD-1 antibody pembrolizumabRecommended phase 2 doseCentral memory T cellsAssociated with anti-tumor activityCD8+ T cellsCD3+ T cellsEGFR-TKI afatinibPD-(L)1 blockadePhase 2 doseTreated with afatinibPhase Ib studyMemory T cellsImmune cell dynamicsControlling brain metastasesCell lung cancerCD4/CD8 T cellsHigh-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 resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities
Janeiro A, Wong E, Jiménez-Sánchez D, de Solorzano C, Lozano M, Teijeira A, Schalper K, Melero I, De Andrea C. Spatially resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities. Journal For ImmunoTherapy Of Cancer 2024, 12: e008589. PMID: 38821717, PMCID: PMC11149121, DOI: 10.1136/jitc-2023-008589.Peer-Reviewed Original ResearchHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machineryUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulatedVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2023
Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non-Small Cell Lung Cancer.
Lopez De Rodas M, Wang Y, Peng G, Gu J, Mino-Kenudson M, Riess J, Velcheti V, Hellmann M, Gainor J, Zhao H, Schalper K. Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non-Small Cell Lung Cancer. Clinical Cancer Research 2023, 30: 998-1008. PMID: 38127300, PMCID: PMC10922461, DOI: 10.1158/1078-0432.ccr-23-2457.Peer-Reviewed Original ResearchNon-small cell lung cancerTIL subsetsCell lung cancerImmune evasion mechanismsSubset of casesLymphocyte infiltration patternsPathology-based approachStrong biomarker potentialTIL markersNSCLC patientsImmunotherapy outcomesLymphocyte patternsLung cancerTumor bedWorse outcomesClinical significanceMost tumorsEvasion mechanismsStromal tissueTumor samplesMultiplexed immunofluorescenceBiomarker potentialTumorsInfiltration patternsImmunotherapy923 Characterization and clinical significance of the intra and inter-tumor spatial immune heterogeneity using 3-dimensional multiplexed phenotyping in non-small cell lung cancer
Rodas M, Frohock Z, Liu X, Vilarino N, Ahumada V, Gettinger S, Murthy Karuturi R, George J, Li Y, Schalper K. 923 Characterization and clinical significance of the intra and inter-tumor spatial immune heterogeneity using 3-dimensional multiplexed phenotyping in non-small cell lung cancer. 2023, a1026-a1026. DOI: 10.1136/jitc-2023-sitc2023.0923.Peer-Reviewed Original Research606 IMpower110: Tertiary lymphoid structures (TLS) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with first-line atezolizumab or chemotherapy
Srivastava M, Gayevskiy V, Ma V, Estay I, Rodas M, Rajendran B, Hoang T, Ballinger M, Amin R, Herbst R, Marinis F, Giaccone G, Jassem J, Spigel D, Schalper K, Koeppen H, Shames D, Johnston R, Giltnane J, Nabet B. 606 IMpower110: Tertiary lymphoid structures (TLS) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with first-line atezolizumab or chemotherapy. 2023, a690-a690. DOI: 10.1136/jitc-2023-sitc2023.0606.Peer-Reviewed Original Research1102 The HLA-E/NKG2A axis is a dominant immunomodulatory pathway associated with distinct tumor microenvironment features in a subset of NSCLC
Ashley K, Iyer K, Kumar R, Cooper Z, Herbst R, Goldberg S, Schalper K. 1102 The HLA-E/NKG2A axis is a dominant immunomodulatory pathway associated with distinct tumor microenvironment features in a subset of NSCLC. 2023, a1213-a1213. DOI: 10.1136/jitc-2023-sitc2023.1102.Peer-Reviewed Original Research1103 Spatial mapping and clinical significance of the CD39/CD73 adenosinergic pathway as a candidate immunotherapy target in non-small cell lung cancer
Ashley K, Iyer K, Kumar R, Cooper Z, Herbst R, Goldberg S, Schalper K. 1103 Spatial mapping and clinical significance of the CD39/CD73 adenosinergic pathway as a candidate immunotherapy target in non-small cell lung cancer. 2023, a1214-a1214. DOI: 10.1136/jitc-2023-sitc2023.1103.Peer-Reviewed Original ResearchTriangular Analysis of Geographical Interplay of Lymphocytes (TriAnGIL): Predicting Immunotherapy Response in Lung Cancer
Arabyarmohammadi S, Corredor G, Zhou Y, López de Rodas M, Schalper K, Madabhushi A. Triangular Analysis of Geographical Interplay of Lymphocytes (TriAnGIL): Predicting Immunotherapy Response in Lung Cancer. Lecture Notes In Computer Science 2023, 14225: 797-807. DOI: 10.1007/978-3-031-43987-2_77.Peer-Reviewed Original Research1434P Machine learning features derived from spatial interaction of immune cell families are associated with survival in NSCLC patients post-immunotherapy
Arabyarmohammadi S, Corredor G, de Rodas Gregorio M, Schalper K, Madabhushi A. 1434P Machine learning features derived from spatial interaction of immune cell families are associated with survival in NSCLC patients post-immunotherapy. Annals Of Oncology 2023, 34: s816. DOI: 10.1016/j.annonc.2023.09.2465.Peer-Reviewed Original ResearchDigital 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 expressionThe β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell functionInternational Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy
Dacic S, Travis W, Redman M, Saqi A, Cooper W, Borczuk A, Chung J, Glass C, Lopez J, Roden A, Sholl L, Weissferdt A, Posadas J, Walker A, Zhu H, Wijeratne M, Connolly C, Wynes M, Bota-Rabassedas N, Sanchez-Espiridion B, Lee J, Berezowska S, Chou T, Kerr K, Nicholson A, Poleri C, Schalper K, Tsao M, Carbone D, Ready N, Cascone T, Heymach J, Sepesi B, Shu C, Rizvi N, Sonett J, Altorki N, Provencio M, Bunn P, Kris M, Belani C, Kelly K, Wistuba I, Committee I. International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy. Journal Of Thoracic Oncology 2023, 18: 1290-1302. PMID: 37702631, DOI: 10.1016/j.jtho.2023.07.017.Peer-Reviewed Original ResearchConceptsPathologic responseViable tumorNeoadjuvant therapyLung cancerClinical trialsInter-rater agreementNeoadjuvant immune checkpoint inhibitorsClinical trial end pointsResected Lung CancerImmune checkpoint inhibitorsTrial end pointsInvasive mucinous adenocarcinomaResidual viable tumorTumor bed areaEosin-stained slidesLung cancer studiesCheckpoint inhibitorsNeoadjuvant treatmentMucinous adenocarcinomaPathologic evaluationStromal inflammationPulmonary pathologistsTumor bedLung tumorsCommon reasonAtezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial
Monjazeb A, Daly M, Luxardi G, Maverakis E, Merleev A, Marusina A, Borowsky A, Mirhadi A, Shiao S, Beckett L, Chen S, Eastham D, Li T, Vick L, McGee H, Lara F, Garcia L, Morris L, Canter R, Riess J, Schalper K, Murphy W, Kelly K. Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Nature Communications 2023, 14: 5332. PMID: 37658083, PMCID: PMC10474145, DOI: 10.1038/s41467-023-40813-w.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerStereotactic ablative radiotherapyEarly-stage non-small cell lung cancerCell lung cancerAblative radiotherapyLung cancerMulti-institutional phase I trialSingle-arm phase IThird of patientsPhase I trialEx vivo stimulationT cell activationInoperable patientsPrimary endpointSecondary endpointsEfficacy signalsI trialT cellsAdaptive immunityCell activationPatientsPhase IPhase IIIEarly responseAtezolizumabNeuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy
Biswas S, Kang K, Ng K, Radivoyevitch T, Schalper K, Zhang H, Lindner D, Thomas A, MacPherson D, Gastman B, Schrump D, Wong K, Velcheti V, Saunthararajah Y. Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy. Cell Reports 2023, 42: 113016. PMID: 37597186, PMCID: PMC10528072, DOI: 10.1016/j.celrep.2023.113016.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerNon-cytotoxic therapiesImmune checkpoint inhibitorsCell lung cancerDNA methyltransferase 1SCLC cellsCytotoxic chemotherapyLung cancerDisseminated small cell lung cancerRepression marksSurvival of miceLineage commitmentCheckpoint inhibitorsResistant therapiesMaster transcription factorMaturation arrestTherapyTranscription factorsClinical compoundsMethyltransferase 1DNMT1 knockdownChemotherapyLineage maturationTranslocation 2Neuroendocrine lineageBSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES
Vilarino N, de Rodas M, Lu B, Goldberg S, Schalper K. BSBM-16 HLA CLASS-I ANTIGEN PRESENTATION MACHINERY AND IFN-γ PATHWAY ALTERATIONS IN LUNG CANCER BRAIN METASTASES. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402438, DOI: 10.1093/noajnl/vdad070.012.Peer-Reviewed Original ResearchLung cancer brain metastasesPrimary lung tumorsImmune checkpoint inhibitorsCancer brain metastasesBrain metastasesPresentation machineryClinicopathologic variablesHLA classTumor cell PD-L1 expressionBackground Immune checkpoint inhibitorsLocal adaptive immune responseHLA Class I AntigenPD-L1 expressionDuration of responseB2MAdaptive immune responsesDistinct immunomodulatory propertiesImmune evasion mechanismsClass I AntigenIFN-γ signalingIRF-1Interferon regulatory factor 1Checkpoint inhibitorsMost patientsWorse survival