2025
Immune dysregulation in glycogen storage disease 1b extends beyond neutropenia
Gehlhaar A, Shouval D, Santiago E, Ling G, McCourt B, Werner L, Yerushalmi B, Konnikova L. Immune dysregulation in glycogen storage disease 1b extends beyond neutropenia. Human Immunology 2025, 86: 111268. PMID: 40037121, DOI: 10.1016/j.humimm.2025.111268.Peer-Reviewed Original ResearchGlycogen storage disease type 1bGlycogen storage disease type 1b patientsImpaired immune cell traffickingClassic treatment strategiesUpregulation of CXCR3Effector memory phenotypeT cell populationsNatural killer cellsSystems immunology approachNon-classical monocytesImmune cell traffickingGlycogen storage disease 1bImmune defectsMemory phenotypeMultiple T cell populationsImmune landscapeRecurrent infectionsKiller cellsImmune dysregulationImmune impairmentImmunophenotypic characterizationSLC37A4 geneControl subjectsTreatment strategiesNeutrophil numbersAltering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates
De Oliveira A, Versteeg L, Briggs N, Adhikari R, Villar M, Redd J, Hotez P, Bottazzi M, Pollet J. Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates. PLOS Neglected Tropical Diseases 2025, 19: e0012809. PMID: 39792959, PMCID: PMC11756802, DOI: 10.1371/journal.pntd.0012809.Peer-Reviewed Original ResearchConceptsAntigen-specific antibodiesMRNA vaccine candidateMRNA vaccinesVaccine candidatesNa-GST-1Plasma membrane-anchoredRobust CD8+ T-cell responsesCD8+ T cell responsesMemory T cell populationsTiters of antigen-specific antibodiesLevels of antigen-specific antibodiesT cell responsesT cell populationsRecombinant Na-GST-1In vivo efficacySubunit vaccine candidateInduce humoral responsesImmunogenicity findingsNeutralizing antibodiesClinical studiesDevelopment of multivalent vaccinesHumoral responseRNA vaccinesImmune responsePeptide presentation
2024
Mutational Features and Tumor Microenvironment Alterations in High-Grade Appendiceal Cancers Treated With Iterative Hyperthermic Intraperitoneal Chemotherapy
Su D, Dhiman A, Bansal V, Zha Y, Shergill A, Polite B, Alpert L, Turaga K, Eng O. Mutational Features and Tumor Microenvironment Alterations in High-Grade Appendiceal Cancers Treated With Iterative Hyperthermic Intraperitoneal Chemotherapy. JCO Precision Oncology 2024, 8: e2400149. PMID: 39259912, PMCID: PMC11432692, DOI: 10.1200/po.24.00149.Peer-Reviewed Original ResearchConceptsHigh-grade appendiceal adenocarcinomaHyperthermic intraperitoneal chemotherapyProgression-free survivalImmunogenomic profilingAppendiceal cancerIntraperitoneal chemotherapyPeritoneal metastasisHigh-grade appendiceal cancerCD8<sup>+</sup> T cellsCytotoxic T cell populationsMutational signaturesAssociated with poor survivalElevated PD-L1Median overall survivalPD-L1 coexpressionPeritoneal tumour depositsT cell populationsTumor microenvironment alterationsNovel treatment approachesWhole-exome sequencingHIPEC treatmentAppendiceal adenocarcinomaOncological outcomesPD-L1Overall survivalClinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas
Swallow M, Micevic G, Zhou A, Carlson K, Foss F, Girardi M. Clinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas. Cancers 2024, 16: 3087. PMID: 39272944, PMCID: PMC11394026, DOI: 10.3390/cancers16173087.Peer-Reviewed Original ResearchT-cell lymphomaPrimary cutaneous gamma/delta T-cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaLymphoproliferative disordersMycosis fungoidesCD8+ cutaneous T-cell lymphomasCutaneous gamma/delta T-cell lymphomaPanniculitis-like T-cell lymphomaGamma/delta T-cell lymphomaCytotoxic T-cell lymphomaT-cell lymphoproliferative disorderAbnormal T-cell populationCutaneous T-cell lymphomaCytotoxic molecule expressionT cell populationsIndicator of prognosisAppropriate treatment planCD8-positiveAggressive entityLymphomatoid papulosisHistological variantsHistopathological differentiationTreatment algorithmCD8Clinical manifestationsA phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA).
Lim J, Aau M, Yeong J, Goh B, Yong W, Soo R, Wong A, Tan D, Chee C, Sundar R, Jeyasekharan A, Wong C, Chen P, Liu H, Yu Q, Tam W, Lee S. A phase Ib/II study of pacritinib, an interleukin 1 receptor associated kinase 1 (IRAK1) inhibitor, in patients (pts) with solid tumors harboring the 1q21.3 copy number amplification (CNA). Journal Of Clinical Oncology 2024, 42: 43-43. DOI: 10.1200/jco.2024.42.23_suppl.43.Peer-Reviewed Original ResearchProgression-free survivalT cell populationsCD8+ T cell populationsCopy number amplificationInterleukin-1 receptor-associated kinase 1Solid tumorsTumor microenvironmentCell populationsDose levelsCD4+ T cell populationRecommended phase II dosePlasma cell-free DNAPeripheral blood mononuclear cells analysisSystemic immune modulationPhase II doseRefractory solid tumorsPhase Ib/II clinical trialDose-expansion cohortDendritic cell populationsMyeloid cell populationsTumor biopsy samplesImmune cell populationsDecreased tumor growthModulated immune cell populationsPreclinical animal modelsHTLV-1 induces an inflammatory CD4+CD8+ T cell population in HTLV-1–associated myelopathy
Maher A, Aristodemou A, Giang N, Tanaka Y, Bangham C, Taylor G, Dominguez-Villar M. HTLV-1 induces an inflammatory CD4+CD8+ T cell population in HTLV-1–associated myelopathy. JCI Insight 2024, 9: e173738. PMID: 38193535, PMCID: PMC10906466, DOI: 10.1172/jci.insight.173738.Peer-Reviewed Original ResearchConceptsHTLV-1-associated myelopathyDP T cellsT cellsHTLV-1Double-positive T cellsAdult T-cell leukemiaT cell populationsT-cell tropismHTLV-1 infectionHuman T-cell leukemia virus type 1Virus type 1T-cell leukemiaCXCR3 expressionPreferential CD4Asymptomatic infectionCNS pathologyIL-6Asymptomatic carriersInflammatory diseasesCytotoxic phenotypeCell leukemiaCell tropismType 1CD4Cell populationsSingle-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases
Yasumizu Y, Takeuchi D, Morimoto R, Takeshima Y, Okuno T, Kinoshita M, Morita T, Kato Y, Wang M, Motooka D, Okuzaki D, Nakamura Y, Mikami N, Arai M, Zhang X, Kumanogoh A, Mochizuki H, Ohkura N, Sakaguchi S. Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases. Cell Genomics 2024, 4: 100473. PMID: 38359792, PMCID: PMC10879034, DOI: 10.1016/j.xgen.2023.100473.Peer-Reviewed Original ResearchConceptsGene programSingle-cell transcriptomic landscapeSingle-cell datasetsCell subpopulationsTranscriptional programsTranscriptomic characterizationCD4<sup>+</sup> T-cell subpopulationsCD4<sup>+</sup> T cellsCellular heterogeneityT cell subpopulationsAutoimmune diseasesCell heterogeneityT cellsPeripheral CD4<sup>+</sup> T cellsCell populationsCD4+ T cell populationCanonical clustersCellsT cell populationsQualitative alterationsT cell heterogeneityGenesSubpopulationsClinical statusCell frequencyIntegrated 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
Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells
Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q, Lopez R, Adelekan-Kamara Y, Fan M, Pober J, Tellides G, Jane-wit D. Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4+ T cells. Frontiers In Immunology 2023, 14: 1248027. PMID: 37915586, PMCID: PMC10616247, DOI: 10.3389/fimmu.2023.1248027.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryHuman skin xenograftsSkin xenograftsT cellsPolyfunctional cytokine responsesSolid organ transplantationT cell subsetsResponse of CD4Expression of ICOST cell populationsHumanized mouse modelPeripheral helper cellsAllograft lossIL-21PD-1Reperfusion injuryCytokine responsesVascular inflammationPolyclonal expansionHelper cellsOrgan transplantationMouse modelClinical problemCostimulatory signalsDistinct subsetsScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis
Mann J, Lucca L, Austin M, Merkin R, Robert M, Al Bawardy B, Raddassi K, Aizenbud L, Joshi N, Hafler D, Abraham C, Herold K, Kluger H. ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis. Journal For ImmunoTherapy Of Cancer 2023, 11: e007358. PMID: 37586769, PMCID: PMC10432652, DOI: 10.1136/jitc-2023-007358.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsT cell subsetsCheckpoint inhibitorsImmune environmentImmune checkpoint inhibitor-induced colitisCheckpoint inhibitor-induced colitisPeripheral immune environmentsStages of colitisTreatment of colitisMerkel cell carcinomaT cell populationsPeripheral blood samplesCourse of progressionT cell receptorMultiple tumor typesAlternative cancer therapyCommon toxicitiesICI colitisTreatment discontinuationAdverse eventsBiologic therapyImmune suppressionCell carcinomaColitisBlood samplesBSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures
2022
The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy.
Micevic G, Bosenberg M, Yan Q. The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy. Clinical Cancer Research 2022, 29: 1173-1182. PMID: 36449280, PMCID: PMC10073242, DOI: 10.1158/1078-0432.ccr-22-0784.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune checkpoint inhibitorsImmune checkpoint therapyT cell exhaustionCheckpoint therapyAntitumor immune responseT cell populationsCell-intrinsic immunityTypes of cancerViral mimicry responseLow response rateCheckpoint inhibitorsCurrent immunotherapiesPancreatic cancerSustained responsePreclinical modelsTreatment outcomesImmune responseEndogenous antigensResponse rateTumor typesMultiple epigenetic regulatorsCritical mediatorLow immunogenicityTherapyCancerPneumonitis in immunotherapy alone vs. chemoimmunotherapy: A systematic review and meta-analysis.
Barbaro A, Siskin M, Grello C, Hernandez A, Dublin J, Breslin S, Punekar S, Velcheti V. Pneumonitis in immunotherapy alone vs. chemoimmunotherapy: A systematic review and meta-analysis. Journal Of Clinical Oncology 2022, 40: e21120-e21120. DOI: 10.1200/jco.2022.40.16_suppl.e21120.Peer-Reviewed Original ResearchNon-small cell lung cancerImmune related adverse eventsImmune checkpoint inhibitorsAdvanced non-small cell lung cancerSevere pneumonitisPD-L1Combination therapyCTLA-4Use of ICIsCombination immune checkpoint inhibitorsLife-threatening complicationsRelated adverse eventsCell lung cancerLung cancer patientsT cell populationsInverse variance weightingGrade pneumonitisCheckpoint inhibitorsInterventional armAdverse eventsCytotoxic chemotherapyImmune suppressionCancer patientsLung cancerClinical trialsA local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
Wu Y, Biswas D, Usaite I, Angelova M, Boeing S, Karasaki T, Veeriah S, Czyzewska-Khan J, Morton C, Joseph M, Hessey S, Reading J, Georgiou A, Al-Bakir M, McGranahan N, Jamal-Hanjani M, Hackshaw A, Quezada S, Hayday A, Swanton C. A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer. Nature Cancer 2022, 3: 696-709. PMID: 35637401, PMCID: PMC9236901, DOI: 10.1038/s43018-022-00376-z.Peer-Reviewed Original ResearchConceptsT cell populationsT cellsLung tissueLung cancerCD8+ T cellsNonsmall-cell lung cancerNonsmall cell lung cancerEffector memory phenotypeT cell compartmentCell lung cancerAssociated with survivalNonmalignant lung tissuesStem-like featuresNontumor lung tissuesT cell biologyHuman lung tissueImmunotherapeutic strategiesMemory phenotypeNatural killerLung tumorsTissue-residentPost-surgeryResident memoryMurine tissuesTumorFirst in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response
Yap TA, Gainor JF, Callahan MK, Falchook GS, Pachynski RK, LoRusso P, Kummar S, Gibney GT, Burris HA, Tykodi SS, Rahma OE, Seiwert TY, Papadopoulos KP, Murphy M, Park H, Hanson A, Hashambhoy-Ramsay Y, McGrath L, Hooper E, Xiao X, Cohen H, Fan M, Felitsky D, Hart C, McComb R, Brown K, Sepahi A, Jimenez J, Zhang W, Baeck J, Laken H, Murray R, Trehu E, Harvey CJ. First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response. Clinical Cancer Research 2022, 28: 3695-3708. PMID: 35511938, PMCID: PMC9433959, DOI: 10.1158/1078-0432.ccr-21-4256.Peer-Reviewed Original ResearchConceptsSubset of patientsPredictive biomarkersPharmacodynamic biomarkersModest objective response rateNon-small cell lung cancer trialsCD4 T cell populationCell lung cancer trialsPhase IObjective response ratePhase II doseAdvanced solid tumorsCD4 T cellsFavorable safety profilePotential predictive biomarkersLung cancer trialsPredictors of responseT cell populationsGreater clinical benefitClinical outcomesClinical benefitSafety profileCancer trialsNivolumabT cellsPatientsPD-L1–PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection
Perry J, Shallberg L, Clark J, Gullicksrud J, DeLong J, Douglas B, Hart A, Lanzar Z, O’Dea K, Konradt C, Park J, Kuchroo J, Grubaugh D, Zaretsky A, Brodsky I, Malefyt R, Christian D, Sharpe A, Hunter C. PD-L1–PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection. Nature Immunology 2022, 23: 743-756. PMID: 35437326, PMCID: PMC9106844, DOI: 10.1038/s41590-022-01170-w.Peer-Reviewed Original ResearchConceptsPD-1ETreg cellsPD-L1Interleukin-10T cellsCell expressionInhibitory receptor PD-1Regulatory T cell populationDevelopment of immunopathologyTreg cell populationRegulatory T cellsEffector T cellsPD-1 interactionReceptor PD-1T cell populationsCell populationsMyeloid cell expressionT cell receptor activationLineage-specific deletionTreg cellsEffector phenotypeInfected miceCell receptor activationInflammatory processEarly interferon
2021
Circulating CD4+ TEMRA and CD4+ CD28− T cells and incident diabetes among persons with and without HIV
Bailin SS, Kundu S, Wellons M, Freiberg MS, Doyle MF, Tracy RP, Justice AC, Wanjalla CN, Landay AL, So-Armah K, Mallal S, Kropski JA, Koethe JR. Circulating CD4+ TEMRA and CD4+ CD28− T cells and incident diabetes among persons with and without HIV. AIDS 2021, 36: 501-511. PMID: 34860194, PMCID: PMC8881388, DOI: 10.1097/qad.0000000000003137.Peer-Reviewed Original ResearchConceptsT cell subsetsIncident diabetesT cellsVeterans Aging Cohort StudyPeripheral mononuclear blood cellsIncident diabetes diagnosisPrevalent diabetes mellitusT effector memoryHIV-negative personsHIV-negative individualsTraditional risk factorsAging Cohort StudyCD28- T cellsSenescent T cellsT cell populationsProportional hazards modelMononuclear blood cellsHigh baseline frequencyCytomegalovirus serostatusCirculating CD4Chart reviewCohort studyEffector memoryInflammatory biomarkersMemory CD4Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease
Friedmann D, Unger S, Keller B, Rakhmanov M, Goldacker S, Zissel G, Frye B, Schupp J, Prasse A, Warnatz K. Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease. Frontiers In Immunology 2021, 11: 616832. PMID: 33613543, PMCID: PMC7892466, DOI: 10.3389/fimmu.2020.616832.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseCommon variable immunodeficiencyBAL fluidB cellsLung diseaseT cellsImmune dysregulationBronchoalveolar lavageHealthy donorsClass-switched memory B cellsLymphocytic interstitial lung diseaseProgressive interstitial lung diseaseLevels of BAFFLike cell subsetSystemic immune dysregulationRegulatory T cellsVideo-assisted thoracoscopyBronchoalveolar lavage fluidT cell populationsPotential immune mechanismsLevels of APRILMemory B cellsB cell interactionsFlow cytometric profilingPotential treatment target
2020
The utility and limitations of B- and T-cell gene rearrangement studies in evaluating lymphoproliferative disorders
Mendoza H, Tormey CA, Rinder HM, Howe JG, Siddon AJ. The utility and limitations of B- and T-cell gene rearrangement studies in evaluating lymphoproliferative disorders. Pathology 2020, 53: 157-165. PMID: 33358756, DOI: 10.1016/j.pathol.2020.09.024.Peer-Reviewed Original ResearchConceptsTCR gene rearrangement analysisGene rearrangement analysisPolymerase chain reactionRearrangement analysisLymphocyte populationsLymphoid malignanciesT-cell receptor gene rearrangement analysisT-cell gene rearrangement studiesTCR gene rearrangement patternsT cell populationsGene rearrangement studiesNext-generation sequencingGene rearrangement patternsLymphoproliferative disordersFrontiers in Celiac Disease
Patel N, Robert ME. Frontiers in Celiac Disease. The American Journal Of Surgical Pathology 2020, 46: e43-e54. PMID: 33739793, DOI: 10.1097/pas.0000000000001639.Peer-Reviewed Original ResearchConceptsCeliac diseaseType II refractory celiac diseaseMonoclonal T-cell populationChildhood viral infectionsDuodenal mucosal histologyImportant autoimmune diseasesRefractory celiac diseaseCommon autoimmune disorderT cell populationsCeliac disease patientsCeliac disease pathogenesisEvaluation of responseCeliac disease manifestationsGluten toleranceDietary glutenGluten exposureMechanisms of diseaseAutoimmune conditionsHLA-DQ2Mucosal histologySymptomatic diseaseInflammatory cascadeInitial diagnosisPatient's symptomsAutoimmune disorders
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