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 ResearchConceptsPD-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 ResearchConceptsTumor 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
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
2014
A preclinical murine model of hepatic metastases.
Soares KC, Foley K, Olino K, Leubner A, Mayo SC, Jain A, Jaffee E, Schulick RD, Yoshimura K, Edil B, Zheng L. A preclinical murine model of hepatic metastases. Journal Of Visualized Experiments 2014, 51677. PMID: 25285458, PMCID: PMC4378377, DOI: 10.3791/51677.Peer-Reviewed Original ResearchConceptsHepatic metastasesMurine modelNumerous murine modelsPreclinical murine modelsTumor immunology researchPancreatic tumor modelPancreatic tumor cellsMurine pancreatic tumor modelMetastatic diseaseClinical conditionsMetastatic processTumor modelTherapy testingTumor cellsCancer treatmentMetastasisHuman cancersImmunology researchLiverModel mimicsPatientsCancerDiseaseMice
2012
Glycolipid Antigens for Treating Hepatic Colorectal Cancer Metastases and Their Effect on the Therapeutic Efficacy of Live Attenuated Listeria monocytogenes
Olino K, Edil BH, Meckel KF, Pan X, Thuluvath A, Pardoll DM, Schulick RD, Yoshimura K, Weber WP. Glycolipid Antigens for Treating Hepatic Colorectal Cancer Metastases and Their Effect on the Therapeutic Efficacy of Live Attenuated Listeria monocytogenes. JAMA Surgery 2012, 147: 480-482. PMID: 22785644, PMCID: PMC4144826, DOI: 10.1001/archsurg.2011.2206.Peer-Reviewed Original ResearchConceptsNatural killer T cellsHepatic colorectal cancer metastasesKiller T cellsColorectal cancer metastasisT cellsNatural Killer T Cell SubsetsCancer metastasisAntitumor activityT cell subsetsAttenuated Listeria monocytogenesPotential of glycolipidsTumor challengeHepatic metastasesMultiple administrationsGlycolipid antigensTherapeutic efficacyListeria monocytogenesActin AAntitumor efficacyMetastasisFurther investigationAdministrationEfficacySpecific glycolipidsSurvival
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 linesTyrosine 23 Phosphorylation-Dependent Cell-Surface Localization of Annexin A2 Is Required for Invasion and Metastases of Pancreatic Cancer
Zheng L, Foley K, Huang L, Leubner A, Mo G, Olino K, Edil BH, Mizuma M, Sharma R, Le DT, Anders RA, Illei PB, Van Eyk JE, Maitra A, Laheru D, Jaffee EM. Tyrosine 23 Phosphorylation-Dependent Cell-Surface Localization of Annexin A2 Is Required for Invasion and Metastases of Pancreatic Cancer. PLOS ONE 2011, 6: e19390. PMID: 21572519, PMCID: PMC3084841, DOI: 10.1371/journal.pone.0019390.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnnexin A2Antibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorBlotting, WesternCancer VaccinesCell Line, TumorCell MembraneCell MovementDisease-Free SurvivalEpithelial-Mesenchymal TransitionFemaleHumansLiverMiceMice, Inbred C57BLNeoplasm InvasivenessNeoplasm MetastasisNeoplasms, ExperimentalPancreatic NeoplasmsPhosphorylationRNA InterferenceTumor Cells, CulturedTyrosineConceptsPancreatic ductal adenocarcinomaAnti-ANXA2 antibodiesPDA metastasisEpithelial-mesenchymal transitionAnnexin A2PDA cellsPost-treatment seraProlongs mouse survivalHigh metastatic potentialCalcium-dependent phospholipid-binding proteinMouse survivalPancreatic cancerDuctal adenocarcinomaEffective therapyProlonged survivalNovel molecular pathwaysANXA2 expressionSerum inhibitsMetastasisPhospholipid-binding proteinEMT processMetastatic potentialAntibody inhibitsPDA developmentNew targets
2009
Integrin α2 Mediates Selective Metastasis to the Liver
Yoshimura K, Meckel KF, Laird LS, Chia CY, Park JJ, Olino KL, Tsunedomi R, Harada T, Iizuka N, Hazama S, Kato Y, Keller JW, Thompson JM, Chang F, Romer LH, Jain A, Iacobuzio-Donahue C, Oka M, Pardoll DM, Schulick RD. Integrin α2 Mediates Selective Metastasis to the Liver. Cancer Research 2009, 69: 7320-7328. PMID: 19738067, PMCID: PMC4857201, DOI: 10.1158/0008-5472.can-09-0315.Peer-Reviewed Original ResearchConceptsHepatic metastasesColorectal cancerPrimary colorectal cancerHuman colorectal cancerIntegrin alpha2Organ-specific metastasisLiver metastasesLung metastasesAntibody blockadeIntegrin alpha2 expressionSelective metastasisIndividual patientsB16 melanomaCollagen type IVMetastasisAlpha2 expressionCell membrane moleculesMetastatic processB16-F0CancerType IVPossible targetsIntegrin α2LiverAlpha2