2025
DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities
Deshmukh M, Brooks V, Roy S, Milette S, Bosenberg M, Micevic G. DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities. Clinical Epigenetics 2025, 17: 71. PMID: 40307913, PMCID: PMC12044936, DOI: 10.1186/s13148-025-01865-5.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseImmune checkpoint moleculesT-cell phenotypeDeregulated expression of oncogenesExpression of MHCDNA methylationCell-intrinsic roleSilencing tumor suppressor genesTumor suppressor geneExpression of oncogenesCheckpoint moleculesImmunological therapiesMelanoma immunotherapyCell immunogenicityAbnormal DNA methylationTumor microenvironmentImmune cellsImproved therapiesMelanomaImmune responseMethylation-based biomarkersTherapeutic opportunitiesDeregulated expressionProliferative signalsTumor migration
2024
Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.
Ma B, Kamle S, Sadanaga T, Lee C, Lee J, Yee D, Zhu Z, Silverman E, DeMeo D, Choi A, Lee C, Elias J. Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis. The Journal Of Immunology 2024, 213: 1279-1291. PMID: 39291933, PMCID: PMC12422026, DOI: 10.4049/jimmunol.2400035.Peer-Reviewed Original ResearchImmune checkpoint moleculesChronic obstructive pulmonary diseaseInhibit adaptive immune responsesAdaptive immune responsesInnate immune responseImmune responseInhibition of innate immune responsesInhibits T cell costimulationGeneration of adaptive immune responsesMacrophage phagocytosisInhibit innate immune responsesChitinase 3-like 1T cell costimulationEpithelial cell deathObstructive pulmonary diseaseCheckpoint moleculesPoor prognosisLung injuryInhibit macrophagesPulmonary diseaseCHI3L1Inflammation pathwaysCancerSHP-2 phosphataseCell deathBeyond T cell exhaustion: TIM-3 regulation of myeloid cells
Dixon K, Lahore G, Kuchroo V. Beyond T cell exhaustion: TIM-3 regulation of myeloid cells. Science Immunology 2024, 9: eadf2223. PMID: 38457514, DOI: 10.1126/sciimmunol.adf2223.Peer-Reviewed Original ResearchConceptsT cell exhaustionTim-3CD8<sup>+</sup> T cellsImmune responseRegulation of myeloid cell functionT cell stemnessTim-3 regulationImmune checkpoint moleculesT cell immunoglobulinCell-extrinsic mechanismsMyeloid cell functionRegulation of myeloid cellsCheckpoint moleculesTreatment of cancerCD4<sup>+</sup>T cellsMyeloid cellsCell-intrinsicCell functionAutoimmunityAutoinflammationCancerImmunoglobulin
2023
Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell A, Huang L, Regan B, Singh V, Vonficht D, Bollhagen A, Wang M, Hou Y, Bod L, Sobel R, Chihara N, Madi A, Anderson A, Regev A, Kuchroo V. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nature Immunology 2023, 24: 1908-1920. PMID: 37828379, PMCID: PMC10864036, DOI: 10.1038/s41590-023-01645-4.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1T cellsMyeloid cellsGenetic deletionPotent antitumor immune responsesCo-inhibitory moleculesExperimental autoimmune encephalomyelitisAntitumor immune responseImmune checkpoint blockadePromising targetSuccessful treatment optionT cell functionCentral nervous systemT cell activationMultiple human cancersAutoimmune neuroinflammationAntitumor immunityAutoimmune encephalomyelitisCheckpoint blockadeCheckpoint moleculesEffector phenotypeAutoimmune diseasesProinflammatory moleculesTissue inflammationTreatment optionsMicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment
Zhou H, Jia W, Lu L, Han R. MicroRNAs with Multiple Targets of Immune Checkpoints, as a Potential Sensitizer for Immune Checkpoint Inhibitors in Breast Cancer Treatment. Cancers 2023, 15: 824. PMID: 36765782, PMCID: PMC9913694, DOI: 10.3390/cancers15030824.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune checkpoint blockadeBreast cancerCheckpoint inhibitorsCheckpoint moleculesImmune checkpointsImmune checkpoint moleculesCancer-associated mortalityBreast cancer treatmentCommon cancer typesCombination regimenAdverse eventsCheckpoint blockadeClinical benefitTherapeutic effectTherapeutic candidateTherapeutic potentialCancer typesCancerCancer treatmentApplication of miRNAsTargetScan databaseMiRNA therapyTreatmentInhibitors
2022
A Randomized Phase 2 Trial of Azacitidine ± Durvalumab as First-line Therapy for Higher-Risk Myelodysplastic Syndromes
Zeidan AM, Boss I, Beach C, Copeland WB, Thompson E, Fox BA, Hasle VE, Ogasawara K, Cavenagh J, Silverman LR, Voso MT, Hellmann A, Tormo M, O’Connor T, Previtali A, Rose S, Garcia-Manero G. A Randomized Phase 2 Trial of Azacitidine ± Durvalumab as First-line Therapy for Higher-Risk Myelodysplastic Syndromes. Blood Advances 2022, 6: 2207-2218. PMID: 34972214, PMCID: PMC9006291, DOI: 10.1182/bloodadvances.2021005487.Peer-Reviewed Original ResearchConceptsHigh-risk myelodysplastic syndromeAdverse eventsArm BArm ASubcutaneous azacitidineMyelodysplastic syndromeTreatment cyclesRandomized phase 2 trialInhibitory immune checkpoint moleculesHematologic adverse eventsMedian overall survivalFirst-line therapyFirst-line treatmentPhase 2 studyPhase 2 trialImmune checkpoint moleculesOverall response rateBone marrow granulocytesAzacitidine monotherapyIntravenous durvalumabCheckpoint moleculesOverall survivalClinical outcomesMarrow granulocytesGrade 3
2021
Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
Barroso-Sousa R, Keenan TE, Li T, Tayob N, Trippa L, Pastorello RG, Richardson III ET, Dillon D, Amoozgar Z, Overmoyer B, Schnitt SJ, Winer EP, Mittendorf EA, Van Allen E, Duda DG, Tolaney SM. Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study. Npj Breast Cancer 2021, 7: 110. PMID: 34433812, PMCID: PMC8387440, DOI: 10.1038/s41523-021-00287-9.Peer-Reviewed Original ResearchMetastatic triple-negative breast cancerTumor-infiltrating lymphocytesTriple-negative breast cancerObjective response ratePD-L1Primary endpointBreast cancerSingle-arm phase II studyHigh tumor-infiltrating lymphocytesLow tumor mutational burdenSafety of cabozantinibPhase II studyImmune checkpoint moleculesHigher pretreatment levelsTumor mutational burdenImmune gene expressionRECIST 1.1Checkpoint moleculesII studyImmunosuppressive cytokinesPartial responseNegative tumorsPositive tumorsTumor immunosuppressionRapid progressionB2M overexpression correlates with malignancy and immune signatures in human gliomas
Zhang H, Cui B, Zhou Y, Wang X, Wu W, Wang Z, Dai Z, Cheng Q, Yang K. B2M overexpression correlates with malignancy and immune signatures in human gliomas. Scientific Reports 2021, 11: 5045. PMID: 33658560, PMCID: PMC7930032, DOI: 10.1038/s41598-021-84465-6.Peer-Reviewed Original ResearchMeSH Keywordsbeta 2-MicroglobulinBiomarkers, TumorBrain NeoplasmsCarcinogenesisCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticGenomicsGliomaHumansImmune Checkpoint ProteinsImmune ToleranceImmunotherapyIsocitrate DehydrogenaseKaplan-Meier EstimateMutationPrognosisPTEN PhosphohydrolaseTumor MicroenvironmentConceptsB2M expressionImmune signaturesM expressionB2MAssociated with immune checkpoint moleculesAssociated with PTEN deletionSuppress anti-tumor immunityAnti-tumor immunityImmune checkpoint moleculesImmunotherapy of gliomaLimited treatment strategiesStromal cell typesCheckpoint moleculesEGFR amplificationClinical characteristicsPTEN deletionPatient prognosisTumor progressionTreatment strategiesGenomic profilingInflammatory activityImmunotherapySomatic mutationsCGGA databasesGlioma
2019
Will deeper characterization of the landscape of immune checkpoint molecules in acute myeloid leukemia bone marrow lead to improved therapeutic targeting?
Vandsemb EN, Kim TK, Zeidan AM. Will deeper characterization of the landscape of immune checkpoint molecules in acute myeloid leukemia bone marrow lead to improved therapeutic targeting? Cancer 2019, 125: 1410-1413. PMID: 30861094, PMCID: PMC6467744, DOI: 10.1002/cncr.32042.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2018
Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer
La Fleur L, Boura V, Alexeyenko A, Berglund A, Pontén V, Mattsson J, Djureinovic D, Persson J, Brunnström H, Isaksson J, Brandén E, Koyi H, Micke P, Karlsson M, Botling J. Expression of scavenger receptor MARCO defines a targetable tumor‐associated macrophage subset in non‐small cell lung cancer. International Journal Of Cancer 2018, 143: 1741-1752. PMID: 29667169, DOI: 10.1002/ijc.31545.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesHigher macrophage infiltrationScavenger receptor MARCOPD-L1Macrophage infiltrationNon-small cell lung cancer (NSCLC) cohortMajority of TAMsNon-small cell lung cancerAvailable immune checkpoint inhibitorsCell lung cancer cohortTumor-associated macrophage subsetsImmunosuppressive tumor-associated macrophagesNew immune targetsImmune checkpoint inhibitorsImmune checkpoint moleculesT cell infiltrationDeath ligand 1Cell lung cancerLung cancer cohortSubset of casesImmune response pathwaysExpression of MARCOProtumor phenotypeCheckpoint inhibitorsCheckpoint molecules
2017
Immune Analysis of Radium-223 in Patients With Metastatic Prostate Cancer
Kim JW, Shin MS, Kang Y, Kang I, Petrylak DP. Immune Analysis of Radium-223 in Patients With Metastatic Prostate Cancer. Clinical Genitourinary Cancer 2017, 16: e469-e476. PMID: 29137877, PMCID: PMC5878980, DOI: 10.1016/j.clgc.2017.10.010.Peer-Reviewed Original ResearchConceptsCell death protein 1Death protein 1Metastatic prostate cancerT cellsProstate cancerPeripheral blood mononuclear cellsFrequency of CD27Frequency of CD8Immune checkpoint moleculesT cell subsetsBlood mononuclear cellsProtein 1Peripheral blood samplesImmune deficiency conditionsSignificant changesMean frequencyEM CD8Checkpoint moleculesFirst doseMemory CD8Osteoblastic metastasesRadium-223Cell subsetsCytokine productionMononuclear cellsIDO1 as a mechanism of adaptive immune resistance to anti-PD1 monotherapy in HNSCC.
Wirth L, Burtness B, Mehra R, Bauman J, Lee J, Smith N, Lefranc-Torres A, Westra W, Bishop J, Faquin W, Lin D, Pai S. IDO1 as a mechanism of adaptive immune resistance to anti-PD1 monotherapy in HNSCC. Journal Of Clinical Oncology 2017, 35: 6053-6053. DOI: 10.1200/jco.2017.35.15_suppl.6053.Peer-Reviewed Original ResearchHPV- HNSCCsPD-L1Clinical responseHNSCC patientsResponse rateAnti-PD-1 monotherapyAnti-PD-1 therapyHuman papillomavirus-associated headAnti-PD-1 blockadeNeck squamous cell carcinomaAdaptive immune resistanceAnti-PD1 monotherapyHPV(-) HNSCC patientsImmunogenic viral antigensImmune checkpoint moleculesPost-treatment biopsiesT cell activityImmune checkpoint pathwaysSquamous cell carcinomaQuantitative PCRImproved response ratesImmune-related genesCheckpoint moleculesPD-1IDO1 expression
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