2024
The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Dugo M, Huang C, Egle D, Bermejo B, Zamagni C, Seitz R, Nielsen T, Thill M, Antón-Torres A, Russo S, Ciruelos E, Schweitzer B, Ross D, Galbardi B, Greil R, Semiglazov V, Gyorffy B, Colleoni M, Kelly C, Mariani G, Del Mastro L, Blasi O, Callari M, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39308141, PMCID: PMC11528202, DOI: 10.1158/1078-0432.ccr-24-0149.Peer-Reviewed Original ResearchPathologic complete response ratePathological complete responseTriple-negative breast cancerRNA-seqI-SPY2Immuno-oncologyBreast cancerPatients treated with pembrolizumabTumor-infiltrating lymphocyte countsPublicly available microarray dataPretreatment core biopsiesImmune checkpoint therapyRNA-seq dataPer-protocol populationAvailable microarray dataI-SPY2 trialPDL1 protein expressionNeoadjuvant atezolizumabNeoadjuvant immunotherapyPlus chemotherapyCheckpoint therapyComplete responseTriple-negativeCore biopsyRT-qPCR data
2023
Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop
Clifton G, Rothenberg M, Ascierto P, Begley G, Cecchini M, Eder J, Ghiringhelli F, Italiano A, Kochetkova M, Li R, Mechta-Grigoriou F, Pai S, Provenzano P, Puré E, Ribas A, Schalper K, Fridman W. Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop. Journal For ImmunoTherapy Of Cancer 2023, 11: e006773. PMID: 37290925, PMCID: PMC10254706, DOI: 10.1136/jitc-2023-006773.Peer-Reviewed Original ResearchConceptsImmune exclusionTumor microenvironmentCheckpoint inhibitorsImmune checkpoint inhibitorsMinority of patientsT cell infiltrationPoor clinical outcomeImmune regulatory pathwaysEffective treatment approachDevelopment of treatmentsVariety of cancersLack of responseCheckpoint therapyImmune profileClinical outcomesClinical benefitPatient outcomesCancer expertsCancer histologyT cellsConsensus definitionTreatment approachesCancer typesRound questionnaireDelphi processA study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2022
The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy.
Micevic G, Bosenberg M, Yan Q. The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy. Clinical Cancer Research 2022, 29: 1173-1182. PMID: 36449280, PMCID: PMC10073242, DOI: 10.1158/1078-0432.ccr-22-0784.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsImmune checkpoint therapyT cell exhaustionCheckpoint therapyAntitumor immune responseT cell populationsCell-intrinsic immunityTypes of cancerViral mimicry responseLow response rateCheckpoint inhibitorsCurrent immunotherapiesPancreatic cancerSustained responsePreclinical modelsTreatment outcomesImmune responseEndogenous antigensResponse rateTumor typesMultiple epigenetic regulatorsCritical mediatorLow immunogenicityTherapyCancerClinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood
Carlisle J, Jansen C, Cardenas M, Sobierajska E, Reyes A, Greenwald R, Del Balzo L, Prokhnevska N, Kucuk O, Carthon B, Mullane P, Osunkoya A, Baumgarten D, Hosseinzadeh F, Wilkinson S, Lake R, Sowalsky A, Liu Y, Master V, Bilen M, Kissick H. Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood. Journal For ImmunoTherapy Of Cancer 2022, 10: e004803. PMID: 35863822, PMCID: PMC9310235, DOI: 10.1136/jitc-2022-004803.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCD8 T cellsCheckpoint therapyT cellsHLA-DRCell carcinomaClinical benefitActivation markers HLA-DRAdvanced renal cell carcinomaPre-existing immune responsesImmune responsePredictor of clinical benefitPeripheral T cell activationPeripheral blood of patientsFlow cytometryT-cell receptor (TCR) sequencingIntratumoral T cellsAntitumor immune responseMarkers HLA-DRAbundant T cellsProportion of CD4Cornerstone of treatmentT cell activationBlood of patientsPredicting therapeutic response
2021
Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages.
Dudzinski S, Bader J, Beckermann K, Young K, Hongo R, Madden M, Abraham A, Reinfeld B, Ye X, MacIver N, Giorgio T, Rathmell J. Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages. The Journal Of Immunology 2021, 207: 3122-3130. PMID: 34772698, PMCID: PMC9095767, DOI: 10.4049/jimmunol.2001152.Peer-Reviewed Original ResearchConceptsAntitumor immunityLean miceAnti-PD-1 checkpoint therapyTumor growthTumor-associated macrophage populationProinflammatory adipokine leptinTumor-infiltrating lymphocytesM1-like phenotypeEffects of leptinInducible NO synthaseMHC class IITumor-Associated MacrophagesInflammatory M1-like phenotypeGreater absolute decreaseMacrophage frequencyProinflammatory adipokinesCheckpoint therapyImmunotherapy efficacyObesity altersTumor burdenInflammatory stateLymphocyte frequenciesObese miceInflammatory cytokinesAdipokine leptinA mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
Fitzgerald B, Connolly KA, Cui C, Fagerberg E, Mariuzza DL, Hornick NI, Foster GG, William I, Cheung JF, Joshi NS. A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Reports Methods 2021, 1: 100080. PMID: 34632444, PMCID: PMC8500377, DOI: 10.1016/j.crmeth.2021.100080.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaNeoantigen expressionTumor-specific CD8 T cellsCD8 T cellsImmune checkpoint therapyInfection-induced inflammationExpression of neoantigensCommon lung cancerLUAD cell linesCheckpoint therapyLung cancerTherapeutic responseT cellsImmune responseMouse modelCell responsesTumor inductionTumorsAdenocarcinomaCell linesNeoantigensKrasFuture studiesExpressionImmunotherapyImmunotherapy Treatment for Triple Negative Breast Cancer
Berger ER, Park T, Saridakis A, Golshan M, Greenup RA, Ahuja N. Immunotherapy Treatment for Triple Negative Breast Cancer. Pharmaceuticals 2021, 14: 763. PMID: 34451860, PMCID: PMC8401402, DOI: 10.3390/ph14080763.Peer-Reviewed Original ResearchTriple-negative breast cancerImmune related adverse eventsBreast cancerMetastatic settingMetastatic triple-negative breast cancerEarly breast cancer settingImmune checkpoint inhibitor therapyBreast cancer settingCheckpoint inhibitor therapyRelated adverse eventsLocal recurrence rateHigh-risk subtypesNegative breast cancerDevelopment of biomarkersTypes of cancerImmunotherapy useAdverse eventsCheckpoint therapyOverall survivalStandard therapySystemic treatmentInhibitor therapyDismal prognosisImmunotherapy treatmentRecurrence rateBlockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
Sun Y, Chen W, Torphy RJ, Yao S, Zhu G, Lin R, Lugano R, Miller EN, Fujiwara Y, Bian L, Zheng L, Anand S, Gao F, Zhang W, Ferrara SE, Goodspeed AE, Dimberg A, Wang XJ, Edil BH, Barnett CC, Schulick RD, Chen L, Zhu Y. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine 2021, 13 PMID: 34321321, PMCID: PMC8749958, DOI: 10.1126/scitranslmed.abc8922.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor binding protein 7Vascular dysfunctionAnti-programmed death-1/Intratumoral effector T cellsTumor vasculatureTumor microenvironmentGrowth factor binding protein 7Tumor-associated endothelial cellsImproved antitumor responsesEffector T cellsDeath-1/Immune checkpoint therapyImmune cell infiltrationFavorable tumor microenvironmentMouse tumor modelsBinding protein 7Checkpoint therapyAntitumor responseCell infiltrationPoor responseT cellsHypoxic tumor microenvironmentTumor perfusionSolid tumorsTherapeutic interventionsIntracranial Complications From Immune Checkpoint Therapy in a Patient With NSCLC and Multiple Sclerosis: Case Report
Lu BY, Isitan C, Mahajan A, Chiang V, Huttner A, Mitzner JR, Wesley SF, Goldberg SB. Intracranial Complications From Immune Checkpoint Therapy in a Patient With NSCLC and Multiple Sclerosis: Case Report. JTO Clinical And Research Reports 2021, 2: 100183. PMID: 34590030, PMCID: PMC8474265, DOI: 10.1016/j.jtocrr.2021.100183.Peer-Reviewed Case Reports and Technical NotesImmune checkpoint inhibitorsMultiple sclerosisRadiation necrosisBrain lesionsWhole-brain radiation therapyImmune checkpoint therapyViable tumor cellsPaucity of dataBrain metastasesCheckpoint inhibitorsMetastatic NSCLCAdverse eventsCheckpoint therapyDurable responsesNeurologic declineRadiographic benefitIntracranial complicationsPathologic findingsAutoimmune disordersAutoimmune diseasesCase reportIntracranial diseaseRadiation therapyStereotactic radiosurgeryAnticancer benefitsDetection of differentially abundant cell subpopulations in scRNA-seq data
Zhao J, Jaffe A, Li H, Lindenbaum O, Sefik E, Jackson R, Cheng X, Flavell RA, Kluger Y. Detection of differentially abundant cell subpopulations in scRNA-seq data. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2100293118. PMID: 34001664, PMCID: PMC8179149, DOI: 10.1073/pnas.2100293118.Peer-Reviewed Original ResearchMeSH KeywordsAgingB-LymphocytesBrainCell LineageCOVID-19CytokinesDatasets as TopicDendritic CellsGene Expression ProfilingGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansMelanomaMonocytesPhenotypeRNA, Small CytoplasmicSARS-CoV-2Severity of Illness IndexSingle-Cell AnalysisSkin NeoplasmsT-LymphocytesTranscriptomeConceptsDA subpopulationsIll COVID-19 patientsImmune checkpoint therapyCOVID-19 patientsSingle-cell RNA sequencing analysisCheckpoint therapyBrain tissueCell subpopulationsRNA sequencing analysisTime pointsSubpopulationsDiseased individualsDistinct phenotypesOriginal studyCell typesAbundant subpopulationSequencing analysisCellsDA measuresPhenotypeImportant differencesNonrespondersPatientsTherapyThe Role of Immune Checkpoint Therapy in Propagating Neurologic Immune-Related Adverse Events: Inducing or "Unmasking" Autoimmunity?
Gardin T, Longbrake EE. The Role of Immune Checkpoint Therapy in Propagating Neurologic Immune-Related Adverse Events: Inducing or "Unmasking" Autoimmunity? Neurology 2021, 96: 733-734. PMID: 33727404, DOI: 10.1212/wnl.0000000000011812.Peer-Reviewed Original Research
2020
Targeted glycan degradation potentiates the anticancer immune response in vivo
Gray MA, Stanczak MA, Mantuano NR, Xiao H, Pijnenborg JFA, Malaker SA, Miller CL, Weidenbacher PA, Tanzo JT, Ahn G, Woods EC, Läubli H, Bertozzi CR. Targeted glycan degradation potentiates the anticancer immune response in vivo. Nature Chemical Biology 2020, 16: 1376-1384. PMID: 32807964, PMCID: PMC7727925, DOI: 10.1038/s41589-020-0622-x.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsAntibodies, MonoclonalB7-H1 AntigenCell Line, TumorHumansHydrolysisImmunoconjugatesImmunotherapyKiller Cells, NaturalMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutModels, MolecularMolecular Targeted TherapyNeuraminidasePolysaccharidesProgrammed Cell Death 1 ReceptorProtein BindingProtein Interaction Domains and MotifsProtein Structure, SecondaryReceptor, ErbB-2Sialic Acid Binding Immunoglobulin-like LectinsSurvival AnalysisT-LymphocytesConceptsImmune checkpoint inhibitor therapyTumor-infiltrating myeloid cellsCheckpoint inhibitor therapyImmune cell infiltrationPowerful treatment optionAnticancer immune responseSurvival of miceSyngeneic breast cancer modelImmune cell activationBreast cancer modelBreast cancer cellsCheckpoint therapyMost patientsInhibitor therapyPD-1Checkpoint receptorsImmune suppressionTreatment optionsCell infiltrationImmune responseMyeloid cellsCancer modelCell activationCertain cancersCancer types
2019
Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets
Stahl M, Goldberg A. Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. Current Oncology Reports 2019, 21: 37. PMID: 30904967, DOI: 10.1007/s11912-019-0781-7.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaImmune checkpoint inhibitionImmune checkpoint inhibitorsCheckpoint inhibitorsCheckpoint inhibitionHypomethylating agentsMyeloid leukemiaCombination of immune checkpoint inhibitionSuccess of immune checkpoint inhibitionClinical trialsEarly-phase clinical trialsCheckpoint inhibitor monotherapyMultiple clinical trialsCheckpoint therapyImmune checkpointsInhibitor monotherapyStandard therapySolid malignanciesImmune targetsTherapeutic efficacyClinical activityTherapeutic landscapeLeukemiaTherapeutic targetLeukemia cells
2018
Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
Leone R, Sun I, Oh M, Sun I, Wen J, Englert J, Powell J. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunology, Immunotherapy 2018, 67: 1271-1284. PMID: 29923026, PMCID: PMC11028354, DOI: 10.1007/s00262-018-2186-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine A2 Receptor AntagonistsAnimalsAntigens, CDCD8-Positive T-LymphocytesColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticImmunotherapyLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMaleMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLProgrammed Cell Death 1 ReceptorReceptor, Adenosine A2AReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsA2AR blockadePD-1T cellsImmune responseA2A receptorsCD39/CD73 axisTumor immune evasionEffector T cellsLAG-3 expressionRegulatory T cellsT cell persistenceTumor bearing miceAdenosine A2A receptorsMurine cancer modelsCoinhibitory receptorsCheckpoint blockadeCheckpoint therapyRegulatory cellsLymph nodesImmunologic responseImmunotherapy regimensInflammatory milieuPharmacologic blockadeA2AR antagonistAdenosine levels
2017
Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.
Sarnaik A, Kluger H, Chesney J, Sethuraman J, Veerapathran A, Simpson-Abelson M, Lotze M, Larsen B, Fischkoff S, Suzuki S, Wang L, Mirgoli M, Fardis M, Curti B. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 3045-3045. DOI: 10.1200/jco.2017.35.15_suppl.3045.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesAdvanced metastatic melanomaMetastatic melanomaTIL productsPrior therapySafety profileIL-2Advanced metastatic melanoma patientsNon-hematologic grade 3Cell therapyPrior systemic therapyAcceptable safety profilePhase 2 studyMetastatic melanoma patientsAdoptive cell therapyEx vivo expansionEnlisted patientsRECIST 1.1Study patientsCheckpoint therapyMedian durationSurgical resectionSystemic therapyAutologous lymphocytesMedian ageEffect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy.
Bernatchez C, Haymaker C, Hurwitz M, Kluger H, Tetzlaff M, Jackson N, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Fanton C, Iacucci E, Aung S, Imperiale M, Liao E, Bentebibel S, Tannir N, Hwu P, Sznol M, Diab A. Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 2545-2545. DOI: 10.1200/jco.2017.35.15_suppl.2545.Peer-Reviewed Original ResearchNKTR-214PD-1 expressionT-cell clonalityTumor microenvironmentNK cellsCell clonalityIL-2 receptor pathwayDays post doseDrug-related AEsImmune-related AEAnti-PD1 therapyCapillary leak syndromePhase 1/2 trialMetastatic solid tumorsFavorable safety profileImmune checkpoint genesSignificant tumor regressionTumor tissue samplesGene expression analysisCytotoxic markersEffector CD8Leak syndromeCheckpoint therapyPrior immunotherapyRegulatory cells
2016
Reply to timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery
Yu JB, Chiang VL. Reply to timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 2016, 122: 3577-3578. PMID: 27495789, DOI: 10.1002/cncr.30243.Peer-Reviewed Original ResearchTiming and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery
Qian JM, Yu JB, Kluger HM, Chiang VL. Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery. Cancer 2016, 122: 3051-3058. PMID: 27285122, PMCID: PMC5030143, DOI: 10.1002/cncr.30138.Peer-Reviewed Original ResearchConceptsMedian percent reductionImmune checkpoint therapyLesional responseStereotactic radiosurgeryCheckpoint therapyLesion volumeAnti-cytotoxic T-lymphocyte-associated protein 4Anti-programmed cell death protein 1T-lymphocyte-associated protein 4Anti-PD-1 therapyGreater median percent reductionsCell death protein 1Administration of immunotherapyWeeks of immunotherapyMelanoma brain metastasesDeath protein 1Type of immunotherapyWilcoxon rank sum testRank sum testNonconcurrent therapyBrain metastasesMelanoma patientsTreatment of cancerSingle institutionPercent reductionImmune checkpoint therapy for non-small-cell lung cancer: an update
Xia B, Herbst RS. Immune checkpoint therapy for non-small-cell lung cancer: an update. Immunotherapy 2016, 8: 279-298. PMID: 26860624, DOI: 10.2217/imt.15.123.Peer-Reviewed Original ResearchConceptsCell lung cancerImmune checkpointsLung cancerCo-inhibitory immune checkpointsRole of immunotherapyImmune checkpoint therapyImmune checkpoint pathwaysSynergistic antitumor activityCheckpoint inhibitorsInhibitory checkpointsCheckpoint therapyL1 antibodyImmune cellsNovel therapiesImmune activityAntagonist antibodyTumor growthTumor microenvironmentTumor cellsTherapyAntitumor activityAntibodiesCancerImmunotherapyCells
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