Featured Publications
Immune Inhibitory Molecule PD-1 Homolog (VISTA) Colocalizes with CD11b Myeloid Cells in Melanoma and Is Associated with Poor Outcomes
Vesely M, Kidacki M, Gaule P, Gupta S, Chan N, Han X, Yeung J, Chen L. Immune Inhibitory Molecule PD-1 Homolog (VISTA) Colocalizes with CD11b Myeloid Cells in Melanoma and Is Associated with Poor Outcomes. Journal Of Investigative Dermatology 2023, 144: 106-115.e4. PMID: 37562584, DOI: 10.1016/j.jid.2023.07.008.Peer-Reviewed Original ResearchConceptsCD11b myeloid cellsImmune inhibitory moleculesPD-L1 expressionVISTA expressionMyeloid cellsFuture potential therapeutic targetsPD-L1/B7Tumor microenvironmentInhibitory moleculesMultiplexed quantitative immunofluorescencePrimary cutaneous melanomaImmunosuppressive tumor microenvironmentNegative prognostic biomarkerCurrent clinical trialsPotential therapeutic targetCause mortalityCritical cell typesPD-L1Poor outcomeTreatment of cancerMelanoma recurrenceCutaneous melanomaClinical trialsPrognostic biomarkerT cellsResistance Mechanisms to Anti-PD Cancer Immunotherapy
Vesely MD, Zhang T, Chen L. Resistance Mechanisms to Anti-PD Cancer Immunotherapy. Annual Review Of Immunology 2022, 40: 45-74. PMID: 35471840, DOI: 10.1146/annurev-immunol-070621-030155.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnti-PD therapyCancer immunotherapyMechanisms of resistanceImmune inhibitory moleculesFraction of patientsResistance mechanismsNormalization cancer immunotherapyAdditional immunotherapyPD-1Clinical evidenceAntigen presentationT cellsSolid tumorsTherapy resistanceH1 pathwayTumor microenvironmentImmunotherapyInhibitory moleculesHematopoietic malignanciesCancer treatmentTherapyPatientsCurrent studyCancer dataMalignancyThe CD8α–PILRα interaction maintains CD8+ T cell quiescence
Zheng L, Han X, Yao S, Zhu Y, Klement J, Wu S, Ji L, Zhu G, Cheng X, Tobiasova Z, Yu W, Huang B, Vesely MD, Wang J, Zhang J, Quinlan E, Chen L. The CD8α–PILRα interaction maintains CD8+ T cell quiescence. Science 2022, 376: 996-1001. PMID: 35617401, DOI: 10.1126/science.aaz8658.Peer-Reviewed Original ResearchConceptsT cell quiescenceT cellsT cell pool sizeMaintenance of CD8Peripheral lymphoid organsCell quiescenceMemory CD8Antigen exposureLymphoid organsActivation phenotypeCD8Specific antigenCD8αInducible deletionCell pool sizeDiverse antigensAntigenMolecular mechanismsBroad repertoireExposureCellsQuiescent stateTumorsMicePILRαPD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus
Han X, Vesely MD, Yang W, Sanmamed MF, Badri T, Alawa J, López-Giráldez F, Gaule P, Lee SW, Zhang JP, Nie X, Nassar A, Boto A, Flies DB, Zheng L, Kim TK, Moeckel GW, McNiff JM, Chen L. PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus. Science Translational Medicine 2019, 11 PMID: 31826980, DOI: 10.1126/scitranslmed.aax1159.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritisAutoantibodiesAutoimmunityDendritic CellsHumansInflammationInterferon Type ILupus Erythematosus, CutaneousLupus Erythematosus, SystemicMembrane ProteinsMice, Inbred BALB CMice, Inbred MRL lprMyeloid CellsNeutrophilsReceptors, Antigen, T-CellSignal TransductionTerpenesUp-RegulationConceptsPlasmacytoid dendritic cellsDiscoid lupus erythematosusSystemic lupus erythematosusCutaneous lupus lesionsPD-1HLupus erythematosusLupus lesionsAutoimmune diseasesKO miceT cellsMyeloid cellsHuman systemic lupus erythematosusBALB/c backgroundCutaneous lupus erythematosusInappropriate immune responseProgression of lupusSystemic autoimmune diseaseImmune cell expansionSuppression of autoimmunityAgonistic monoclonal antibodyDeath-1 homologCutaneous lupusProinflammatory neutrophilsDendritic cellsDLE lesionsHIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease
Little A, Chen P, Vesely M, Khan R, Fiedler J, Garritano J, Islam F, McNiff J, Craft J. HIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease. JCI Insight 2023, 8: e166076. PMID: 37526979, PMCID: PMC10543720, DOI: 10.1172/jci.insight.166076.Peer-Reviewed Original ResearchConceptsCutaneous lupus erythematosusLupus skin diseaseT cellsSkin diseasesCytotoxic signatureInflammatory infiltrateHIF-1Tissue damageKidney-infiltrating T cellsSkin-infiltrating T cellsAutoimmune skin diseaseHIF-1 inhibitionSkin tissue damageLupus erythematosusSystemic diseaseTissue inflammationGranzyme BMouse modelInflammatory gene programDiseaseProtein levelsInfiltratesSkin environmentGene programPresent study
2024
Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulated
2023
Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights
Noelle R, Lines J, Lewis L, Martell R, Guillaudeux T, Lee S, Mahoney K, Vesely M, Boyd-Kirkup J, Nambiar D, Scott A. Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights. Frontiers In Oncology 2023, 13: 1225081. PMID: 37795437, PMCID: PMC10547146, DOI: 10.3389/fonc.2023.1225081.Commentaries, Editorials and LettersImmune checkpoint proteinsImmune checkpointsImmune systemT-lymphocyte antigen-4Cell death protein 1V-domain immunoglobulin suppressorDeath protein 1CD28 family membersAnti-VISTA antibodyT cell activationImportant homeostatic functionsVISTA blockadePD-1Proinflammatory changesImmune effectsMyeloid suppressionAntigen-4CTLA-4Immune cellsT cellsImmune responsePreclinical studiesClinical developmentHomeostatic functionsMyeloid lineage
2021
Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategiesA Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer
2020
In silico analysis of the immunological landscape of pituitary adenomas
Yeung JT, Vesely MD, Miyagishima DF. In silico analysis of the immunological landscape of pituitary adenomas. Journal Of Neuro-Oncology 2020, 147: 595-598. PMID: 32236778, PMCID: PMC7261241, DOI: 10.1007/s11060-020-03476-x.Peer-Reviewed Original ResearchConceptsPituitary adenomasImmunological landscapeImmune cellsM2 macrophagesPituitary tumorsAdenoma subtypesSilent pituitary tumorsMemory T cellsImmune cell typesDifferent immunotherapiesHigh CD8Immune infiltratesImmune landscapeSilent tumorsGH tumorsImmunological compositionMacrophage fractionT cellsMast cellsTumor subtypesSolid tumorsSubclinical casesAdenomasTumorsSubtypesGetting Under the Skin: Targeting Cutaneous Autoimmune Disease.
Vesely MD. Getting Under the Skin: Targeting Cutaneous Autoimmune Disease. The Yale Journal Of Biology And Medicine 2020, 93: 197-206. PMID: 32226348, PMCID: PMC7087062.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCutaneous autoimmune diseasesAutoimmune diseasesCutaneous autoimmunityImmune systemEffector armT cellsTherapeutic strategiesChimeric autoantibody receptor T cellsRegulatory armLow-dose interleukin-2Regulatory T cellsExcessive immune activationReceptor T cellsGreater treatment efficacyBroad immunosuppressantsCytokine blockadeTolerogenic vaccinesCostimulatory blockadeDisease remissionImmune activationInflammatory pathwaysImmune homeostasisInterleukin-2Treatment efficacyNormal skin
2018
Chapter One Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies
Han X, Vesely MD. Chapter One Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies. International Review Of Cytology 2018, 342: 1-25. PMID: 30635089, PMCID: PMC6487201, DOI: 10.1016/bs.ircmb.2018.07.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsT cellsT-lymphocyte antigen-4Monoclonal antibodiesInhibitory T cell receptorsCostimulatory receptor CD137Immunostimulatory monoclonal antibodiesUse of immunotherapeuticsT cell receptorAntitumor immunityDeath-1Antigen-4Immune surveillanceAgonist antibodyCostimulatory receptorsF. Macfarlane BurnetCancer cellsAntibodiesCancerReceptorsMacfarlane BurnetCellsGITRCD137CD27OX40
2013
Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy
Vesely MD, Schreiber RD. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Annals Of The New York Academy Of Sciences 2013, 1284: 1-5. PMID: 23651186, PMCID: PMC3648872, DOI: 10.1111/nyas.12105.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune systemTumor-specific antigensHuman cancer patientsTumor-promoting actionsNascent tumor cellsAntitumor immunityTumor immunityCancer immunosurveillanceChronic inflammationPersonalized cancer therapyImmunogenic variantsCancer immunotherapyCancer patientsCancer immunoeditingT cellsAnimal modelsTumor variantsTumor progressionTumor cellsCancer cellsImmunityCancer therapyCancerAntigenImmunoselection