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 ResearchQuantitative 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 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 ResearchInternational 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 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 outcomesRole of HLA class-I antigen peptide loading complex components in immune evasion and treatment sensitivity in human lung cancer.
Costantini A, Ranjan K, Ferrone S, Schalper K. Role of HLA class-I antigen peptide loading complex components in immune evasion and treatment sensitivity in human lung cancer. Journal Of Clinical Oncology 2023, 41: 2623-2623. DOI: 10.1200/jco.2023.41.16_suppl.2623.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsHLA classSelective downregulationShorter OSICI resistanceMarker levelsStromal cellsLow marker levelTumor antigen recognitionEffector T cellsT cell infiltrationT cell levelsProtein levelsPeptide loading complexEarly-stage tumorsHuman lung cancerPeptide-HLA complexesLevels of TAPDeterminants of sensitivityLow CD8Checkpoint inhibitorsHuman NSCLCPresentation machineryClinicopathologic variablesLung cancerGenomic 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