2023
Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development
Tawbi H, Sullivan R, Feltquate D, LaVallee T, Rizvi N, Sharon E, Sosman J, Kluger H. Society for Immunotherapy of Cancer (SITC) checkpoint inhibitor resistance definitions: efforts to harmonize terminology and accelerate immuno-oncology drug development. Journal For ImmunoTherapy Of Cancer 2023, 11: e007309. PMID: 37487665, PMCID: PMC10373737, DOI: 10.1136/jitc-2023-007309.Peer-Reviewed Original ResearchSurvival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian S, Sznol M, McDermott D, Kluger H, Carvajal R, Sharfman W, Brahmer J, Lawrence D, Atkins M, Powderly J, Leming P, Lipson E, Puzanov I, Smith D, Taube J, Wigginton J, Kollia G, Gupta A, Pardoll D, Sosman J, Hodi F. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2023, 41: 943-954. PMID: 36750016, DOI: 10.1200/jco.22.02272.Peer-Reviewed Original ResearchLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2022
Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cells
2021
Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade
Berry S, Giraldo NA, Green BF, Cottrell TR, Stein JE, Engle EL, Xu H, Ogurtsova A, Roberts C, Wang D, Nguyen P, Zhu Q, Soto-Diaz S, Loyola J, Sander IB, Wong PF, Jessel S, Doyle J, Signer D, Wilton R, Roskes JS, Eminizer M, Park S, Sunshine JC, Jaffee EM, Baras A, De Marzo AM, Topalian SL, Kluger H, Cope L, Lipson EJ, Danilova L, Anders RA, Rimm DL, Pardoll DM, Szalay AS, Taube JM. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science 2021, 372 PMID: 34112666, PMCID: PMC8709533, DOI: 10.1126/science.aba2609.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansImmune Checkpoint ProteinsMacrophagesMaleMelanomaMiddle AgedPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptors, Cell SurfaceSingle-Cell AnalysisSOXE Transcription FactorsT-Lymphocyte SubsetsTreatment OutcomeTumor MicroenvironmentConceptsAnti-programmed cell death 1Anti-PD-1 blockadePD-1 blockadeCell death 1Tissue-based biomarkersLong-term survivalTumor tissue sectionsDeath-1PD-1PD-L1Immunoregulatory moleculesT cellsIndependent cohortMyeloid cellsMelanoma specimensMultiple cell typesTissue sectionsLow/BlockadeCell typesDistinct expression patternsExpression patternsImagingCD8Foxp3
2019
Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma
Wong PF, Wei W, Gupta S, Smithy JW, Zelterman D, Kluger HM, Rimm DL. Multiplex quantitative analysis of cancer-associated fibroblasts and immunotherapy outcome in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 194. PMID: 31337426, PMCID: PMC6651990, DOI: 10.1186/s40425-019-0675-0.Peer-Reviewed Original ResearchConceptsProgression-free survivalBest overall responseSmooth muscle actinOverall survivalCell countQuantitative immunofluorescenceImmune markersImmunotherapy outcomesMelanoma patientsSignificant progression-free survivalAnti-PD-1 therapyAbsence of immunotherapyPretreatment tumor specimensImmune checkpoint blockadeCell death 1Cancer-associated fibroblast (CAF) populationNegative prognostic biomarkerCancer-associated fibroblastsWhole tissue sectionsOverall responseOS associationCAF parametersCheckpoint blockadeImmune dysregulationDeath-1
2016
Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases
Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg S, Kluger HM, Chiang VL. Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases. Cancer Immunology Research 2016, 4: 481-487. PMID: 26994250, DOI: 10.1158/2326-6066.cir-15-0238.Peer-Reviewed Original ResearchConceptsStereotactic radiosurgeryBrain metastasesInitiation of immunotherapyPD-1 mAbImmune-modulating therapyModalities of treatmentRadiologic progressionSurgical resectionSystemic therapyDeath-1Radiologic findingsMetastatic malignancyReactive astrocytosisPathologic examinationTreatment regimensHistopathologic examinationWall infiltrationT lymphocytesPatientsTumor progressionMonoclonal antibodiesBiologic interactionsRadiation-induced changesImmunotherapyMalignancy
2014
Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal Of Clinical Oncology 2014, 32: 1020-1030. PMID: 24590637, PMCID: PMC4811023, DOI: 10.1200/jco.2013.53.0105.Peer-Reviewed Original ResearchConceptsLong-term safetyOverall survivalToxicity ratesTumor regressionResponse durationOngoing randomized clinical trialsDurable tumor remissionNivolumab-treated patientsMedian overall survivalMedian response durationPD-1 blockadeObjective tumor regressionMaintenance of responseCell death 1Randomized clinical trialsSimilar patient populationsActivated T cellsDrug discontinuationIntravenous nivolumabNivolumab therapyNivolumab treatmentTreatment discontinuationObjective responseAdvanced melanomaDeath-1
2013
Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up.
Drake C, McDermott D, Sznol M, Choueiri T, Kluger H, Powderly J, Smith D, Sankar V, Gutierrez A, Wigginton J, Kollia G, Gupta A, Atkins M. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up. Journal Of Clinical Oncology 2013, 31: 4514-4514. DOI: 10.1200/jco.2013.31.15_suppl.4514.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOverall survivalDrug-related AEsGrade 3 pneumonitisMedian overall survivalAcceptable safety profilePhase III trialsPD-1 ligandsPhase I trialLong-term patientsPD-1 receptorImmune checkpoint receptorsRenal cell carcinomaLong-term safetyT cell activationPopulation of ptsPrior therapyTreatment discontinuationAdverse eventsIII trialsMedian durationUnacceptable toxicityComplete responseDeath-1I trial