2023
BSBM-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
2022
Impact of HIV infection on clinical outcomes among people diagnosed with head and neck cancer.
Salahuddin S, Cohen O, Wu M, Irizarry J, Vega T, Gan G, Deng Y, Isaeva N, Schalper K, Mehra S, Yarbrough W, Emu B. Impact of HIV infection on clinical outcomes among people diagnosed with head and neck cancer. Journal Of Clinical Oncology 2022, 40: e18080-e18080. DOI: 10.1200/jco.2022.40.16_suppl.e18080.Peer-Reviewed Original ResearchOropharyngeal squamous cell carcinomaCD8 T cell infiltrationPD-L1 expressionUninfected patientsT cell infiltrationPoor outcomeHNC patientsInsurance statusRace/ethnicityMedian survivalQuantitative immunofluorescenceIndependent predictorsClinical outcomesViral loadCell infiltrationNeck cancerAnatomic sitesTobacco useMultivariate analysisLow PD-L1 expressionCombination antiretroviral therapy eraTumor microenvironmentAntiretroviral therapy eraMedian CD4 countHIV viral load
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 patients
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 therapyTrial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer.
LoRusso P, Pilat M, Santa-Maria C, Connolly R, Roesch E, Afghahi A, Han H, Nanda R, Wulf G, Assad H, Park H, Dees E, Force J, Noonan A, Brufsky A, Abramson V, Haley B, Buys S, Sharon E, Schalper K. Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer. Journal Of Clinical Oncology 2020, 38: tps1102-tps1102. DOI: 10.1200/jco.2020.38.15_suppl.tps1102.Peer-Reviewed Original ResearchPositive breast cancerPo bidPARP inhibitionBreast cancerImmune responseOpen-label phase II clinical trialAdaptive anti-tumor immune responsesAnti-tumor immune responsePhase II clinical trialMarked lymphocyte infiltrationPD-1 blockadePD-L1 expressionPre-treatment biopsiesProgression-free survivalAntitumor immune responseImmune checkpoint blockadeMajority of patientsBRCA 1/2 mutationsTumor immune contextureBiopsy time pointsHomologous DNA repairPARP inhibitor olaparibMonotherapy armCombination armImmune contexture
2018
Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand (PD-L)-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing
Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, Plodkowski A, Long N, Sauter JL, Rekhtman N, Hollmann T, Schalper KA, Gainor JF, Shen R, Ni A, Arbour KC, Merghoub T, Wolchok J, Snyder A, Chaft JE, Kris MG, Rudin CM, Socci ND, Berger MF, Taylor BS, Zehir A, Solit DB, Arcila ME, Ladanyi M, Riely GJ, Schultz N, Hellmann MD. Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand (PD-L)-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. Journal Of Clinical Oncology 2018, 36: jco.2017.75.338. PMID: 29337640, PMCID: PMC6075848, DOI: 10.1200/jco.2017.75.3384.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsDurable clinical benefitTumor mutation burdenPD-L1 expressionCell lung cancerTargeted Next-Generation SequencingWhole-exome sequencingLung cancerNext-generation sequencingPartial response/stable diseaseUse of ICIsAnti-programmed death-1Response/stable diseaseSolid Tumors version 1.1Anti-programmed cell deathProgression-free survivalResponse Evaluation CriteriaSubset of patientsPredictors of responseMultivariable predictive modelDetailed clinical annotationLack of benefitStable diseaseCheckpoint inhibitorsDurable responses
2016
Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer
Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Modern Pathology 2016, 30: 340-349. PMID: 27834350, PMCID: PMC5334264, DOI: 10.1038/modpathol.2016.186.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPD-L1Immune cellsImmune cell PD-L1 expressionNon-small cell lung cancerNon-small cell lung cancer (NSCLC) casesCell lung cancer casesTumor cellsPD-L1 assessmentStromal immune cellsPD-L1 positivityCell lung cancerLung cancer patientsLung cancer casesRepresentative tumor areasPathologist scoresLikelihood of responseConcordance correlation coefficientRabbit monoclonal antibodyIntraclass correlation coefficientCancer patientsLung cancerImmunohistochemistry slidesCancer casesTumor tissueMeta-analysis of tumor PD-L1 expression as a predictive biomarker of benefit from PD-1/PD-L1 axis inhibitors in solid tumors.
Khunger M, Rakshit S, Schalper K, Elson P, Pennell N, Stevenson J, Velcheti V. Meta-analysis of tumor PD-L1 expression as a predictive biomarker of benefit from PD-1/PD-L1 axis inhibitors in solid tumors. Journal Of Clinical Oncology 2016, 34: 11603-11603. DOI: 10.1200/jco.2016.34.15_suppl.11603.Peer-Reviewed Original ResearchQuantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays
2015
PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer
Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunology Research 2015, 3: 326-332. PMID: 25527356, PMCID: PMC4390454, DOI: 10.1158/2326-6066.cir-14-0133.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesPD-L1 expressionPathologic complete responseNeoadjuvant chemotherapyPD-L1Breast cancerDeath 1 ligand 1PD-L1 protein expressionYale-New Haven HospitalHigh PD-L1Antitumor immune activitySubset of patientsTriple-negative patientsBreast cancer patientsTriple-negative statusImmune checkpoint proteinsImmune regulatory moleculesNew Haven HospitalSignificant multivariate modelRabbit monoclonal antibodyTILs correlateComplete responseImmune therapyCancer patientsImmune activity
2014
PD-L1 expression and tumor-infiltrating lymphocytes
Schalper KA. PD-L1 expression and tumor-infiltrating lymphocytes. OncoImmunology 2014, 3: e29288. PMID: 25083339, PMCID: PMC4106164, DOI: 10.4161/onci.29288.Peer-Reviewed Original Research
2013
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic value