2024
Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchMeSH KeywordsActinsBiomarkers, TumorCTLA-4 AntigenHumansMelanomaProgrammed Cell Death 1 ReceptorProteomicsTumor MicroenvironmentConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumors
2023
Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCD8-Positive T-LymphocytesCytokinesDendritic CellsDisease Models, AnimalHumansImmunotherapyInterleukin-12MiceNeoplasmsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeLenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCytokinesMelanomaMicePhenylurea CompoundsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentVascular Endothelial Growth Factor AConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2020
Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance
Olino K, Park T, Ahuja N. Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance. Seminars In Cancer Biology 2020, 65: 114-122. PMID: 31911188, DOI: 10.1016/j.semcancer.2020.01.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAntineoplastic AgentsB7-H1 AntigenCombined Modality TherapyCTLA-4 AntigenEpigenesis, GeneticEpigenetic RepressionHumansImmunotherapyNeoplasmsProgrammed Cell Death 1 ReceptorConceptsResponse ratePeripheral T-cell lymphomaTriple-negative breast cancerLarge B-cell lymphomaDurable response rateEffective standard therapyDeath protein 1Solid organ tumorsInhibitory immune receptorsT-cell lymphomaNegative breast cancerB-cell lymphomaAdvanced malignanciesMost patientsStandard therapyClinical efficacyCommon malignancyHepatobiliary cancersTherapeutic optionsNeck cancerOrgan tumorsInitial respondersOvarian cancerProstate cancerBreast cancer
2019
PD-1 Blockade in Advanced Adrenocortical Carcinoma.
Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RKG, Capanu M, Zamarin D, Saltz LB, Ariyan CE, Untch BR, O'Reilly EM, Gopalan A, Berger MF, Olino K, Segal NH, Reidy-Lagunes DL. PD-1 Blockade in Advanced Adrenocortical Carcinoma. Journal Of Clinical Oncology 2019, 38: 71-80. PMID: 31644329, PMCID: PMC7351334, DOI: 10.1200/jco.19.01586.Peer-Reviewed Original ResearchConceptsAdvanced adrenocortical carcinomaObjective response rateAdrenocortical carcinomaObjective responseResponse rateMedian progression-free survivalMismatch repair-deficient statusTreatment-related grade 3Disease control rateManageable safety profileMedian overall survivalPD-1 blockadePercent of patientsPhase II studyPrimary end pointProgression-free survivalDurable antitumor activityLimited treatment optionsMicrosatellite stable tumorsPrior therapyAdverse eventsII studyMedian durationOverall survivalStandard therapyPatterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma
Klemen ND, Wang M, Feingold PL, Cooper K, Pavri SN, Han D, Detterbeck FC, Boffa DJ, Khan SA, Olino K, Clune J, Ariyan S, Salem RR, Weiss SA, Kluger HM, Sznol M, Cha C. Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 196. PMID: 31340861, PMCID: PMC6657062, DOI: 10.1186/s40425-019-0672-3.Peer-Reviewed Original ResearchConceptsThree-year progression-free survivalProgression-free survivalDisease-specific survivalFive-year disease-specific survivalPatterns of failureDurable progression-free survivalLocal therapyStereotactic body radiotherapyMetastatic melanomaNew metastasesPatient selectionIndependent radiological reviewOngoing complete responseResultsFour hundred twentyEvidence of diseaseCNS metastasisCPI treatmentImmunotherapy failureCheckpoint inhibitorsMost patientsProgressive diseaseRadiological reviewComplete responsePD-1PD-L1
2015
PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors
Soares KC, Rucki AA, Wu AA, Olino K, Xiao Q, Chai Y, Wamwea A, Bigelow E, Lutz E, Liu L, Yao S, Anders RA, Laheru D, Wolfgang CL, Edil BH, Schulick RD, Jaffee EM, Zheng L. PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors. Journal Of Immunotherapy 2015, 38: 1-11. PMID: 25415283, PMCID: PMC4258151, DOI: 10.1097/cji.0000000000000062.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPD-1 blockadeT cellsObjective responsePD-L1PDA patientsPD-1/PD-L1 blockadePD-1/PD-L1 pathwayCytotoxic T-lymphocyte antigen-4Effector T-cell infiltrationPD-1 antibody monotherapyPD-L1 antibody therapySingle-agent checkpoint inhibitorsT-lymphocyte antigen-4Tumor microenvironmentMurine pancreatic ductal adenocarcinomaAddition of vaccineCTLA-4 pathwayImmune suppressive cellsImmune-suppressive signalsPDA tumor microenvironmentPD-L1 blockadeLow-dose cyclophosphamideCD8 T lymphocytesPD-1 antibody
2011
Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases
Olino K, Wada S, Edil BH, Pan X, Meckel K, Weber W, Slansky J, Tamada K, Lauer P, Brockstedt D, Pardoll D, Schulick R, Yoshimura K. Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases. Annals Of Surgical Oncology 2011, 19: 597-607. PMID: 21979110, PMCID: PMC4498288, DOI: 10.1245/s10434-011-2037-0.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntigens, DifferentiationAntigens, NeoplasmAntineoplastic Agents, AlkylatingCarcinomaCD8-Positive T-LymphocytesCell Line, TumorColonic NeoplasmsCTLA-4 AntigenCyclophosphamideFemaleImmunotherapyInterferon-gammaListeria monocytogenesLiver NeoplasmsLymphocyte CountMiceMice, Inbred BALB CProgrammed Cell Death 1 ReceptorStatistics, NonparametricSurvival AnalysisT-Lymphocytes, RegulatoryConceptsT cell responsesEffector memory T cellsMetastatic colorectal cancerMemory T cellsTumor rechallengeColorectal cancerT cellsTumor-specific T-cell responsesAntigen-specific effector CD8Tumor-specific cytotoxic CD8Antitumor T-cell responsesEffective antitumor T-cell responsesMemory T cell responsesHepatic colorectal cancer metastasesCurrent immunotherapeutic strategiesImmune checkpoint moleculesColorectal cancer metastasisCTLA-4 expressionTumor-associated antigensTumor associated antigensCT26 colon cancer cell lineL. monocytogenes strainsColon cancer cell linesImmunologic milieuCancer cell lines