2025
PD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation
Kidacki M, Cho C, Lopez-Giraldez F, Huang B, He J, Gaule P, Chen L, Vesely M. PD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation. Journal Of Investigative Dermatology 2025 PMID: 39983979, DOI: 10.1016/j.jid.2025.01.030.Peer-Reviewed Original ResearchCutaneous squamous cell carcinomaPD-L1 expressionT cell infiltrationPD-L1Squamous cell carcinomaVISTA expressionPD-1HCell carcinomaT cellsBlockade of PD-1Proliferation marker Ki-67Multiplexed quantitative immunofluorescencePD-L1 coexpressionTreatment of cutaneous squamous cell carcinomaControl T cellsPreclinical cancer studiesMyeloid cell functionImmunosuppressive microenvironmentPD-1Receptor antagonismKi-67Individual tumorsGranzyme B.Clinical trialsCancer clinical trials
2024
Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors.
Thomas S, Pico B, Henick B, Leidner R, Samhouri Y, Isaacs J, Weiss J, Hurwitz M, Grewal J, Luke J, Chattopadhyay S, Wang Y, Motta M, Murray J, Barton D, Pinchasik D, MacBeath G, Moser J. Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors. Journal Of Clinical Oncology 2024, 42: 2542-2542. DOI: 10.1200/jco.2024.42.16_suppl.2542.Peer-Reviewed Original ResearchT-cell receptor-engineered T-cell therapyLoss of heterozygositySolid tumorsHLA-A*02:01HLA matchingHLA allelesPatients evaluated to dateFirst-in-human clinical trialDose level 1Dose level 3Pre-identify patientsTarget HLA alleleAntitumor T cellsT-cell therapyLoss of heterozygosity testingT-cell attackMaster protocolProportion of patientsScreening protocolCombination of HLAHLA LOHHLA lossImmunosuppressive microenvironmentMAGE-A1HLA typingIntegrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Therapeutic Advances In Hematology 2024, 15: 20406207241257904. PMID: 38883163, PMCID: PMC11180421, DOI: 10.1177/20406207241257904.Peer-Reviewed Original ResearchHigher-risk myelodysplastic syndromesAcute myeloid leukemiaBone marrowMutation statusImmune landscapeImmunological landscapeAnti-PD-L1 antibody durvalumabHR-MDS patientsWild-type acute myeloid leukemiaTP53-mutant acute myeloid leukemiaMutant acute myeloid leukemiaAzacitidine-based therapyWild-type patientsImmune checkpoint proteinsImmune checkpoint expressionT cell populationsWild-typeStatistically significant decreaseAZA therapyImmunosuppressive microenvironmentPD-L1Mutant patientsDNA methylation arraysCheckpoint expressionMyelodysplastic syndrome
2023
Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Li B, Li Y, Zhou H, Xu Y, Cao Y, Cheng C, Peng J, Li H, Zhang L, Su K, Xu Z, Hu Y, Lu J, Lu Y, Qian L, Wang Y, Zhang Y, Liu Q, Xie Y, Guo S, Mehal W, Yu D. Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma. Hepatology 2023, 79: 289-306. PMID: 37540187, PMCID: PMC10789383, DOI: 10.1097/hep.0000000000000553.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPatient-derived xenograftsTransarterial chemoembolizationF1 subtypeMolecular classificationAnti-programmed cell death-1 therapyNovel molecular classificationCancer patient therapyCheckpoint inhibitorsBevacizumab treatmentPD-L1Immunosuppressive microenvironmentRNA sequencingPatient cohortHepatocellular carcinomaImmunological characteristicsTherapeutic strategiesPotential respondersPatient therapyYM-155Prognosis predictionPrecision therapySingle-cell RNA sequencingMetabolic subtypesTumor microenvironmentPTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.
Exposito F, Redrado M, Houry M, Hastings K, Molero-Abraham M, Lozano T, Solorzano J, Sanz-Ortega J, Adradas V, Amat R, Redin E, Leon S, Legarra N, Garcia J, Serrano D, Valencia K, Robles-Oteiza C, Foggetti G, Otegui N, Felip E, Lasarte J, Paz-Ares L, Zugazagoitia J, Politi K, Montuenga L, Calvo A. PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells. Cancer Research 2023, 83: 2513-2526. PMID: 37311042, DOI: 10.1158/0008-5472.can-22-3023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLung squamous carcinomaAnti-PD-1 therapyRegulatory T cellsCell lung cancerImmunosuppressive microenvironmentLung cancerImmunotherapy resistanceT cellsWorse progression-free survivalCell death protein 1PTEN lossAnti-TGFβ antibodyConversion of CD4PI3K/AKT/mTOR pathwayProgression-free survivalDeath protein 1Treatment of miceImmunosuppressive tumor microenvironmentPTEN/PI3K/AKT/mTOR pathwayAKT/mTOR pathwayPD-L1TLR agonistsTumor rejectionSquamous carcinoma
2022
Cancer Immunoediting in the Era of Immuno-oncology.
Gubin MM, Vesely MD. Cancer Immunoediting in the Era of Immuno-oncology. Clinical Cancer Research 2022, 28: 3917-3928. PMID: 35594163, PMCID: PMC9481657, DOI: 10.1158/1078-0432.ccr-21-1804.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCancer immunoeditingImmune-tumor cell interactionsCancer immunotherapyAbsence of immunotherapyDurable clinical responsesT cell biologyCell interactionsImmunotherapy resistanceClinical responseImmunosuppressive microenvironmentTumor immunogenicityImmuno-oncologyClinical dataPreclinical modelsImmunoeditingImmunotherapyHuman patientsImmune systemTumor microenvironmentCancerCancer progressionClinical subspecialtyImmunogenicityMicroenvironmentPatientsGenetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy
Rangel R, Pickering CR, Sikora AG, Spiotto MT. Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy. Frontiers In Immunology 2022, 13: 840923. PMID: 35154165, PMCID: PMC8829003, DOI: 10.3389/fimmu.2022.840923.Peer-Reviewed Original ResearchConceptsOral premalignant lesionsImmunosuppressive microenvironmentProgression of OPLsOral cavity cancerGenomic alterationsImmune microenvironmentOral cancerOSCC progressionInflammatory environmentPremalignant lesionsSpecific genomic changesOral premalignancyTherapeutic approachesNovel biomarkersMalignant transformationMicroenvironmental changesCancerProgressionGenomic changesMicroenvironmentAlterationsGenetic changesPremalignancyTherapyLesions
2020
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis
Zhang Y, Lazarus J, Steele NG, Yan W, Lee HJ, Nwosu ZC, Halbrook CJ, Menjivar RE, Kemp SB, Sirihorachai VR, Velez-Delgado A, Donahue K, Carpenter ES, Brown KL, Irizarry-Negron V, Nevison AC, Vinta A, Anderson MA, Crawford HC, Lyssiotis CA, Frankel TL, Bednar F, di Magliano M. Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis. Cancer Discovery 2020, 10: 422-439. PMID: 31911451, PMCID: PMC7224338, DOI: 10.1158/2159-8290.cd-19-0958.Peer-Reviewed Original ResearchConceptsPancreatic cancerTreg depletionPancreatic carcinogenesisRegulatory T cellsT cell responsesMyeloid cell recruitmentMouse pancreatic cancerNew therapeutic approachesSmooth muscle actinPromotion of carcinogenesisImmune suppressionImmunosuppressive microenvironmentReceptors CCR1T cellsTherapeutic approachesCell recruitmentMouse modelMyeloid cellsMuscle actinRelated commentaryTumor progressionTregsTumor microenvironmentCancerFibroblast subsets
2019
IMMU-28. TARGETING IMMUNOSUPPRESSIVE MYELOID DERIVED SUPPRESSOR CELLS VIA MIF/CD74 SIGNALING AXIS TO ATTENUATE GBM GROWTH
Alban T, Bayik D, Otvos B, Grabowski M, Ahluwalia M, Bucala R, Vogelbaum M, Lathia J. IMMU-28. TARGETING IMMUNOSUPPRESSIVE MYELOID DERIVED SUPPRESSOR CELLS VIA MIF/CD74 SIGNALING AXIS TO ATTENUATE GBM GROWTH. Neuro-Oncology 2019, 21: vi125-vi125. PMCID: PMC6847354, DOI: 10.1093/neuonc/noz175.521.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorTumor growthTumor microenvironmentMIF receptorM-MDSCsCytokine macrophage migration inhibitory factorGeneration of MDSCsTumor-infiltrating MDSCsMigration inhibitory factorMCP-1 secretionPersistent tumor growthImmune cell recognitionFuture clinical assessmentImmunosuppressive myeloidMDSC generationMDSC inhibitionMonocytic MDSCsPotent immunosuppressionMDSC functionSuppressor cellsImmunosuppressive microenvironmentImmune suppressionPoor prognosisImmune cellsCo-culture systemGlutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone R, Zhao L, Englert J, Sun I, Oh M, Sun I, Arwood M, Bettencourt I, Patel C, Wen J, Tam A, Blosser R, Prchalova E, Alt J, Rais R, Slusher B, Powell J. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366: 1013-1021. PMID: 31699883, PMCID: PMC7023461, DOI: 10.1126/science.aav2588.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzo CompoundsCaproatesCD8-Positive T-LymphocytesCitric Acid CycleEnergy MetabolismFemaleGlucoseGlutamineImmunologic MemoryImmunotherapy, AdoptiveLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalTumor EscapeTumor MicroenvironmentConceptsEffector T cellsT cellsTumor immune evasionCancer cellsPotent antitumor responsesImmune cell functionAntitumor responseImmunosuppressive microenvironmentTumor immunotherapyCancer immunotherapyMice suppressesImmune evasionCell functionOxidative metabolismGlycolytic metabolismGlutamine antagonistImmunotherapyMetabolic characteristicsMetabolic programsTumorsMetabolic checkpointDivergent changesMetabolismCellsAntagonism
2014
Chronic inflammation drives glioma growth: cellular and molecular factors responsible for an immunosuppressive microenvironment
Ha E, Antonios J, Soto H, Prins R, Yang I, Kasahara N, Liau L, Kruse C. Chronic inflammation drives glioma growth: cellular and molecular factors responsible for an immunosuppressive microenvironment. Neuroimmunology And Neuroinflammation 2014, 1: 66-76. DOI: 10.4103/2347-8659.139717.Peer-Reviewed Original ResearchImmunosuppressive microenvironmentTumor massPatient's own immune systemGrade of malignancyCell typesCharacteristics of gliomasTumor microenvironmentGene therapyInflammatory microenvironmentChronic inflammationGlioma patientsImmune systemGliomaGlioma growthDisease initiationMicroenvironmentTumorMolecular factorsPatientsCellsMalignancyTherapyInflammationClearanceImmune-
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