2024
EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer
Ermer T, Kim S, Goldberg S, Zolfaghari E, Blasberg J, Boffa D, Herbst R, Politi K, Schalper K, Dacic S, Woodard G. EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2024, 19: s543-s544. DOI: 10.1016/j.jtho.2024.09.1007.Peer-Reviewed Original ResearchImmune Cell Dynamics in EGFR-Mutated 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 EGFR-Mutated NSCLC Treated With Afatinib and Pembrolizumab: Results From a Phase IB Study. JTO Clinical And Research Reports 2024, 5: 100706. PMID: 39318388, PMCID: PMC11420451, 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 cellsQuantitative 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
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 patternsImmunotherapy606 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 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 Research923 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 ResearchAtezolizumab 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 lineageDeep 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 outcomesGenomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer
Ravi A, Hellmann M, Arniella M, Holton M, Freeman S, Naranbhai V, Stewart C, Leshchiner I, Kim J, Akiyama Y, Griffin A, Vokes N, Sakhi M, Kamesan V, Rizvi H, Ricciuti B, Forde P, Anagnostou V, Riess J, Gibbons D, Pennell N, Velcheti V, Digumarthy S, Mino-Kenudson M, Califano A, Heymach J, Herbst R, Brahmer J, Schalper K, Velculescu V, Henick B, Rizvi N, Jänne P, Awad M, Chow A, Greenbaum B, Luksza M, Shaw A, Wolchok J, Hacohen N, Getz G, Gainor J. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer. Nature Genetics 2023, 55: 807-819. PMID: 37024582, PMCID: PMC10181943, DOI: 10.1038/s41588-023-01355-5.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerAnti-PD-1/PD-L1 agentsCheckpoint blockade responsePD-L1 agentsTumor intrinsic subtypesCheckpoint inhibitorsCheckpoint blockadeTreatment landscapeImmunotherapy outcomesBlockade responseCohortBiological determinantsGenomic subgroupsEnhanced responseMolecular featuresWhole exomeCancerProminent associationOutcomesAssociationResponseNumber of associations
2022
2MO First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in metastatic non-small cell lung cancer (mNSCLC): Clinical outcomes and biomarker analyses from CheckMate 592
Gettinger S, Schenker M, De Langen J, Fischer J, Morgensztern D, Ciuleanu T, Beck T, De Castro Carpeno J, Schumann C, Yang X, Telivala B, Deschepper K, Nadal E, Schalper K, Spires T, Balli D, Nassar A, Karam S, Bhingare A, Spigel D. 2MO First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) in metastatic non-small cell lung cancer (mNSCLC): Clinical outcomes and biomarker analyses from CheckMate 592. Immuno-Oncology Technology 2022, 16: 100107. DOI: 10.1016/j.iotech.2022.100107.Peer-Reviewed Original Research148 TAP2 deficiency mediates adaptive immune evasion and immunotherapy resistance in human non-small cell lung cancer
Ranjan K, Deen I, Rodas M, Gianino N, Ferrone S, Schalper K. 148 TAP2 deficiency mediates adaptive immune evasion and immunotherapy resistance in human non-small cell lung cancer. 2022, a161-a161. DOI: 10.1136/jitc-2022-sitc2022.0148.Peer-Reviewed Original ResearchOA09.04 Spatial Mapping and Clinical Significance of the LAG-3/FGL1 Pathway in Non-small Cell Lung Cancer Using High-Dimensional Tissue Imaging
Desai S, Sanmamed M, Wang J, Schalper K. OA09.04 Spatial Mapping and Clinical Significance of the LAG-3/FGL1 Pathway in Non-small Cell Lung Cancer Using High-Dimensional Tissue Imaging. Journal Of Thoracic Oncology 2022, 17: s25. DOI: 10.1016/j.jtho.2022.07.049.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 patientsTumor Microenvironment: Immune Effector and Suppressor Imbalance
Sheehan K, Schalper K. Tumor Microenvironment: Immune Effector and Suppressor Imbalance. Current Cancer Research 2021, 1-25. DOI: 10.1007/978-3-030-74028-3_1.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor microenvironmentNon-small cell lung cancerHuman non-small cell lung cancerCell lung cancerImmune evasion pathwaysPatient selection strategiesImmune cell interactionsBroad clinical useAnti-cancer therapyMechanism of actionCheckpoint inhibitorsImmune stimulatoryLung cancerIndividual patientsImmune featuresCurrent evidenceImmune effectorsTherapeutic targetingClinical useFuture cancer therapeuticsSuppressor signalsCancer therapeuticsCell interactionsPatientsP15.04 A Phase I/IB Trial of Pembrolizumab and Trametinib Focused on Advanced KRAS Mutant Non-Small Cell Lung Cancer
Riess J, Schalper K, Kelly K, Shimoda M, Luxardi G, Merleev A, Monjazeb A, Danenberg K, Maverakis E, Gandara D. P15.04 A Phase I/IB Trial of Pembrolizumab and Trametinib Focused on Advanced KRAS Mutant Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2021, 16: s345. DOI: 10.1016/j.jtho.2021.01.541.Peer-Reviewed Original Research
2020
Atezolizumab plus stereotactic ablative therapy for medically inoperable patients with early-stage non-small cell lung cancer.
Kelly K, Daly M, Mirhadi A, Lara F, Garcia L, Chen S, Eastham D, Wiegner E, Riess J, Schalper K, Monjazeb A. Atezolizumab plus stereotactic ablative therapy for medically inoperable patients with early-stage non-small cell lung cancer. Journal Of Clinical Oncology 2020, 38: 9011-9011. DOI: 10.1200/jco.2020.38.15_suppl.9011.Peer-Reviewed Original ResearchNon-small cell lung cancerStereotactic ablative radiation therapyEarly-stage non-small cell lung cancerImmune checkpoint inhibitorsStage non-small cell lung cancerPD-L1 expressionCell lung cancerFlat dosingLung cancerInoperable early-stage non-small cell lung cancerRandomized phase III trialEarly-stage NSCLC patientsQuantitative immunofluorescenceAdditional efficacy outcomesCycles of atezolizumabDose level 2Grade 3 pneumonitisMedian age 77Mild toxicity profileSerial blood analysesPhase II doseGrade 3 rashPhase III trialsStage NSCLC patientsAblative radiation therapy
2019
MA25.02 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 Research