2024
High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis
Park S, Roh T, Tanaka Y, Kim Y, Park S, Kim T, Eom S, Park T, Park I, Kim S, Kim J. High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis. Neoplasia 2024, 60: 101116. PMID: 39724755, PMCID: PMC11729681, DOI: 10.1016/j.neo.2024.101116.Peer-Reviewed Original ResearchConceptsP16<sup>INK4a</sup> expressionImmune cell infiltrationTumor cellsCell infiltrationImmunologically active tumor microenvironmentInfiltration of T cellsActive tumor microenvironmentTERT promoter mutationsExtended overall survivalIsocitrate dehydrogenase (IDH)-wildtypeSecretion of chemokinesSenescent phenotypeMalignant brain tumorsIn vitro studiesEGFR amplificationOverall survivalTumor microenvironmentCDKN2A/2B deletionT cellsPrognostic markerImprove prognosisP16INK4a expressionPromoter mutationsTumorBrain tumorsA phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer.
Christenson E, Mahadevan D, Kazmi S, Manda S, Sohal D, Hutson T, Fu S, Martz A, Kordahi S, Barbu E, Flies D, Langermann S, Chisamore M, Gutierrez M, Matrana M, Spira A, Wadlow R, Guha U, Myint H, Le D. A phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer. Journal Of Clinical Oncology 2024, 42: 2538-2538. DOI: 10.1200/jco.2024.42.16_suppl.2538.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune cell infiltrationOvarian cancerColorectal cancerICI therapyCell infiltrationAdvanced metastatic colorectal cancerPromote immune cell infiltrationResistance to ICI therapyEffector memory T cellsPeripheral blood immunophenotypingPhase 1b/2 studyDose of pembrolizumabData cut-offMetastatic colorectal cancerMetastatic solid tumorsMemory T cellsColorectal cancer subjectsImmune cell functionHuman IgG1 Fc domainAnti-tumor activityTumor extracellular matrixModified toxicity probability intervalExtracellular matrixCheckpoint inhibitorsAcute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice
Hussain H, Elumalai N, Sampath N, Shamaladevi N, Hajjar R, Druyan B, Rashed A, Ramamoorthy R, Kenyon N, Jayakumar A, Paidas M. Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice. Viruses 2024, 16: 832. PMID: 38932125, PMCID: PMC11209276, DOI: 10.3390/v16060832.Peer-Reviewed Original ResearchMurine hepatitis virus-1Inflammatory bowel diseaseCeliac diseaseImmune cell infiltrationDevelopment of targeted therapeutic strategiesGoblet cell hyperplasiaHistopathological alterationsRestore tissue homeostasisAmeliorating inflammatory responsesLung complicationsGastrointestinal complicationsMucosal inflammationLymphoid hyperplasiaCell hyperplasiaCardiovascular abnormalitiesMurine modelCell infiltrationInflammatory profileRestore tissue architectureVillous atrophyEpithelial integrityMouse modelPathological featuresTherapeutic strategiesExposure to SARS-CoV-2Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection
Cinco I, Napier E, Rhoades N, Davies M, Allison D, Kohama S, Bermudez L, Winthrop K, Fuss C, Spindel E, Messaoudi I. Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection. MBio 2024, 15: e00829-24. PMID: 38771046, PMCID: PMC11237422, DOI: 10.1128/mbio.00829-24.Peer-Reviewed Original ResearchConceptsNTM pulmonary diseaseIncreased disease severityNontuberculous mycobacteriaDisease severityBacterial DNAAged animalsAntigen-specific T cellsPulmonary diseaseAssociated with increased disease severityDysregulated macrophage responsePersistence of bacterial DNALack of animal modelsRhesus macaquesSingle-cell RNA sequencingNontuberculous mycobacterial infectionsImmune cell infiltrationRhesus macaque modelBacterial loadAged rhesus macaquesTesting novel therapeuticsRight caudal lobeLower respiratory microbiomeYears of ageMAH infectionMicrobial communitiesSingle-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury. Physiology 2024, 39: 1314. DOI: 10.1152/physiol.2024.39.s1.1314.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisAcute lung injuryChronic obstructive pulmonary diseaseAcute respiratory distress syndromeAnalysis of cell-cell communicationVEGF-DMicrovascular nicheSingle-cell RNA-seqLung injury modelSingle-cell RNA-seq analysisLung injuryCell-cell communicationLigand-receptor pairsLPS-induced lung injury modelRNA-seqAdjacent cell typesPulmonary diseaseInjury modelHuman lung endothelial cellsBarrier functionImmune cell infiltrationTumor necrosis factor-aRespiratory distress syndromeLung vascular integrityGene expressionMulti-omics analysis reveals immune features associated with immunotherapy benefit in squamous cell lung cancer patients from Phase III Lung-MAP S1400I trial
Parra E, Zhang J, Duose D, Gonzalez-Kozlova E, Redman M, Chen H, Manyam G, Kumar G, Zhang J, Song X, Lazcano R, Marques-Piubelli M, Laberiano-Fernandez C, Rojas F, Zhang B, Taing L, Jhaveri A, Geisberg J, Altreuter J, Michor F, Provencher J, Yu J, Cerami E, Moravec R, Kannan K, Luthra R, Alatrash G, Huang H, Xie H, Patel M, Nie K, Harris J, Argueta K, Lindsay J, Biswas R, Van Nostrand S, Kim-Schulze S, Gray J, Herbst R, Wistuba I, Gettinger S, Kelly K, Bazhenova L, Gnjatic S, Lee J, Zhang J, Haymaker C. Multi-omics analysis reveals immune features associated with immunotherapy benefit in squamous cell lung cancer patients from Phase III Lung-MAP S1400I trial. Clinical Cancer Research 2024, 30: 1655-1668. PMID: 38277235, PMCID: PMC11016892, DOI: 10.1158/1078-0432.ccr-23-0251.Peer-Reviewed Original ResearchConceptsChromosome copy-number variationsOverall survivalMultiplex immunofluorescenceMulti-omics analysisAssociated with superior progression-free survivalNCounter PanCancer Immune Profiling PanelSquamous cell lung cancer patientsSuperior progression-free survivalTreated with nivolumab monotherapyAssociated with worse overall survivalNon-small cell carcinomaAssociated with worse survivalCell lung cancer patientsCold immune microenvironmentProgression-free survivalImmune Profiling PanelRegulatory T cellsPhase III trialsResponse to ICIImmune cell infiltrationHigher immune scoresImmune cell densityLung cancer patientsWhole-exome sequencingImmune gene expression profiles
2023
The association between the amino acid transporter LAT1, tumor immunometabolic and proliferative features and menopausal status in breast cancer
Ramshankar G, Liu R, Perry R. The association between the amino acid transporter LAT1, tumor immunometabolic and proliferative features and menopausal status in breast cancer. PLOS ONE 2023, 18: e0292678. PMID: 37819900, PMCID: PMC10566702, DOI: 10.1371/journal.pone.0292678.Peer-Reviewed Original ResearchConceptsL-type amino acid transporter 1Menopausal statusPrognostic effectLAT1 expressionBreast cancerTumor proliferationAmino acid transporter LAT1Immune cell infiltrationHigh LAT1 expressionAmino acid transporter 1Worse patient outcomesKaplan-Meier modelBreast cancer prognosisPatient survival probabilityPositron emission tomography-computed tomography (PET-CT) imagesSpecific essential amino acidsClinical factorsClinical parametersCell infiltrationPatient outcomesSystemic metabolismCancer prognosisBody compositionProliferative featuresCancer typesHepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model
Kuhn T, Kahl V, Wang Y, Berz A, Shewarega A, Santana J, Antoch G, Chapiro J, Schlachter T, Madoff D. Hepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model. Journal Of Vascular And Interventional Radiology 2023, 34: 2162-2172.e2. PMID: 37634850, DOI: 10.1016/j.jvir.2023.08.024.Peer-Reviewed Original ResearchConceptsPortal vein embolizationFuture liver remnantVein embolizationLiver remnantCirrhotic liverStandardized future liver remnantNon-cirrhotic groupImmune cell infiltrationNon-cirrhotic liverN-butyl cyanoacrylateT-testFemale Yorkshire pigsLarge animal modelLarge animal studiesStudent's t-testCirrhotic groupEmbolized lobeBaseline percentageHepatic hypertrophyCell infiltrationBaseline CTKi-67Preclinical studiesInstitutional Animal CareFLR increaseA novel defined pyroptosis-related gene signature predicts prognosis and correlates with the tumour immune microenvironment in lung adenocarcinoma
Chen Z, Ge L, Xu S, Li Q, Zhou L. A novel defined pyroptosis-related gene signature predicts prognosis and correlates with the tumour immune microenvironment in lung adenocarcinoma. Scientific Reports 2023, 13: 9921. PMID: 37337018, PMCID: PMC10279685, DOI: 10.1038/s41598-023-36720-1.Peer-Reviewed Original ResearchConceptsPyroptosis-related genesTumor-infiltrating immune cellsTumor mutational burdenLung adenocarcinomaImmune cellsMutational burdenPrognostic signaturePyroptosis-related gene signatureTumor microenvironmentGene Expression Omnibus (GEO) cohortSelection operator CoxImmune cell infiltrationRole of pyroptosisIndependent prognostic biomarkerTumor immune microenvironmentCox regression modelImmune checkpoint regulatorsCancer-related deathCancer Genome Atlas (TCGA) databaseSpearman correlation analysisFuture studiesImmune microenvironmentCell infiltrationLUAD patientsCommon causeDickkopf1 Promotes Pulmonary Fibrosis upon Bleomycin-Induced Lung Injury
Sung E, Park M, Henegariu O, Sime P, Chae W. Dickkopf1 Promotes Pulmonary Fibrosis upon Bleomycin-Induced Lung Injury. American Journal Of Pathology 2023, 193: 1130-1142. PMID: 37263344, PMCID: PMC10477954, DOI: 10.1016/j.ajpath.2023.05.009.Peer-Reviewed Original ResearchConceptsLung injuryImmune cell infiltrationLung inflammationCell infiltrationCollagen depositionBleomycin-Induced Lung InjuryOrchestration of inflammationRole of DKK1Patient's lung tissueSmooth muscle actinGrowth factor-β1Myofibroblast marker αDKK1 protein expressionTissue repair processAntibody administrationPulmonary inflammationPulmonary fibrosisProfibrotic cytokinesDKK1 levelsAttractive molecular targetFibrosis modelLung tissueTissue injuryTissue fibrosisFactor-β1A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltrationA novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma
Chen Y, Lin X, Zou X, Qian Y, Liu Y, Wang R, Wang X, Yu X, Liu C, Cheng H. A novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma. BMC Gastroenterology 2023, 23: 113. PMID: 37024802, PMCID: PMC10080823, DOI: 10.1186/s12876-023-02748-w.Peer-Reviewed Original ResearchConceptsTumor-infiltrating immune cellsExpression of OX40Risk score modelImmune cellsIdentified OX40Immune checkpointsOverall survivalScoring systemRisk scoreClinical specimensExpression of immune checkpoint genesCD8+ T cellsImmune checkpoint gene expressionSomatic mutationsProtein expressionHigh-risk score groupImmunogenic cell deathCheckpoint gene expressionImmune checkpoint expressionImmune checkpoint genesImmune cell infiltrationNaive B cellsCox regression analysisAssociated with increased survival ratesRisk scoring system
2022
Correlation between PD-L1 expression of the tumour cells and lymphocytes infiltration in the invasive front of urothelial carcinoma
Chen X, Chen H, Lin R, Li Y, Guo Y, Chen Q, Zhang Y, Cai G, Hu M, Chen G. Correlation between PD-L1 expression of the tumour cells and lymphocytes infiltration in the invasive front of urothelial carcinoma. Journal Of Clinical Pathology 2022, 77: 61-67. PMID: 36319076, PMCID: PMC10804014, DOI: 10.1136/jcp-2021-207795.Peer-Reviewed Original ResearchPD-L1 expressionUrothelial carcinomaOverall survivalPD-L1Tumor cellsCell infiltrationInvasive frontPD-1/PD-L1 signal pathwayNon-small cell lung cancerOS of patientsInvasive bladder urothelial carcinomaPD-L1 groupIndependent prognostic factorT cell infiltrationAdvanced bladder cancerCell lung cancerImmune cell infiltrationMore T cellsFirst new drugT cell functionBladder urothelial carcinomaMeans of immunohistochemistryLymphocyte infiltrationPD-1Prognostic factorsFusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
Michikawa C, Gopalakrishnan V, Harrandah AM, Karpinets TV, Garg RR, Chu RA, Park YP, Chukkapallia SS, Yadlapalli N, Erikson-Carter KC, Gleber-Netto FO, Sayour E, Progulske-Fox A, Chan , Wu X, Zhang J, Jobin C, Wargo JA, Pickering CR, Myers JN, Silver N. Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1). Neoplasia 2022, 31: 100813. PMID: 35834946, PMCID: PMC9287628, DOI: 10.1016/j.neo.2022.100813.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAdjacent normal tissuesWhole-exome sequencingNormal tissuesNeck cancerOral tongue squamous cell carcinoma patientsTongue squamous cell carcinoma patientsSquamous cell carcinoma patientsTumor samplesPD-L1 mRNA expressionPD-L1 protein expressionOral tongue SCCCell carcinoma patientsOral tongue cancerImmune cell infiltrationPD-L1 mRNATumor immune microenvironmentNeck SCC cell linesNeck cancer cell linesSCC cell linesDevelopment of headCell linesCancer cell linesTongue SCCCarcinoma patientsBasic principles of neuroimmunology
Yoshida TM, Wang A, Hafler DA. Basic principles of neuroimmunology. Seminars In Immunopathology 2022, 44: 685-695. PMID: 35732977, DOI: 10.1007/s00281-022-00951-7.Peer-Reviewed Original ResearchConceptsNeuro-immune interactionsCentral nervous systemImmune privilegeCerebrospinal fluidCNS-resident immune cellsImmune-derived cytokinesResident T cellsImmune cell infiltrationImmune-privileged organMeningeal lymphatic systemIntroduction of antigenImmune compartmentNeuroinflammatory diseasesNeurological functionCNS homeostasisCell infiltrationHarmful inflammationImmune cellsPeripheral organsT cellsImmune responseLeukocyte traffickingNervous systemImmune systemLymphatic systemThe feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II–III and metastatic breast cancers
Anderson KS, Erick TK, Chen M, Daley H, Campbell M, Colson Y, Mihm M, Zakka LR, Hopper M, Barry W, Winer EP, Dranoff G, Overmoyer B. The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II–III and metastatic breast cancers. Breast Cancer Research And Treatment 2022, 194: 65-78. PMID: 35482127, PMCID: PMC9046531, DOI: 10.1007/s10549-022-06562-y.Peer-Reviewed Original ResearchConceptsBreast cancer vaccinesAutologous GM-CSFBreast cancerMetastatic diseaseGM-CSFStage IICancer vaccinesTumor cellsEvidence of diseaseStart of vaccinationInjection site reactionsMetastatic breast cancerUpper respiratory symptomsImmune cell infiltrationRole of vaccinationReplication-defective adenoviral vectorEvaluable patientsMethodsTumor cellsStable diseaseWeekly vaccinationsJoint painProgressive diseaseRespiratory symptomsFifth injectionTRIAL REGISTRATION
2021
Comparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model
Doemel LA, Santana JG, Savic LJ, Gaupp FML, Borde T, Petukhova-Greenstein A, Kucukkaya AS, Schobert IT, Hamm CA, Gebauer B, Walsh JJ, Rexha I, Hyder F, Lin M, Madoff DC, Schlachter T, Chapiro J, Coman D. Comparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model. European Radiology 2021, 32: 2437-2447. PMID: 34718844, PMCID: PMC9359419, DOI: 10.1007/s00330-021-08337-3.Peer-Reviewed Original ResearchConceptsDrug-eluting embolicsImmune cell infiltrationAntigen-presenting cellsBicarbonate infusionConventional TACEDEE-TACETransarterial chemotherapyCell infiltrationImmune cellsPeritumoral infiltrationT lymphocytesIntratumoral immune cell infiltrationTumor modelRabbit VX2 liver tumor modelImmunological tumor microenvironmentVX2 liver tumor modelIntra-arterial therapyIntra-arterial treatmentRabbit VX2 tumor modelLiver tumor modelTumor-bearing rabbitsVX2 tumor modelMann-Whitney U testIntratumoral presenceTransarterial chemoembolizationInfiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
Backman M, La Fleur L, Kurppa P, Djureinovic D, Elfving H, Brunnström H, Mattsson J, Lindberg A, Pontén V, Eltahir M, Mangsbo S, Gulyas M, Isaksson J, Jirström K, Kärre K, Leandersson K, Mezheyeuski A, Pontén F, Strell C, Lindskog C, Botling J, Micke P. Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer. The Journal Of Pathology 2021, 255: 243-256. PMID: 34339045, DOI: 10.1002/path.5772.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune cell infiltrationHigh immune cell infiltrationCell infiltrationNK cellsImmune classPlasma cellsLow immune cell infiltrationEra of immunotherapyCell lung cancerImmune cell markersTumor mutational loadImmune response-related genesInnate immune responseImmune cell analysisClinicopathologic characteristicsPD-L1Immune activationImmune classificationNSCLC casesImmune patternsLung cancerImmune cellsClinical backgroundImmune responseBlockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
Sun Y, Chen W, Torphy RJ, Yao S, Zhu G, Lin R, Lugano R, Miller EN, Fujiwara Y, Bian L, Zheng L, Anand S, Gao F, Zhang W, Ferrara SE, Goodspeed AE, Dimberg A, Wang XJ, Edil BH, Barnett CC, Schulick RD, Chen L, Zhu Y. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine 2021, 13 PMID: 34321321, PMCID: PMC8749958, DOI: 10.1126/scitranslmed.abc8922.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor binding protein 7Vascular dysfunctionAnti-programmed death-1/Intratumoral effector T cellsTumor vasculatureTumor microenvironmentGrowth factor binding protein 7Tumor-associated endothelial cellsImproved antitumor responsesEffector T cellsDeath-1/Immune checkpoint therapyImmune cell infiltrationFavorable tumor microenvironmentMouse tumor modelsBinding protein 7Checkpoint therapyAntitumor responseCell infiltrationPoor responseT cellsHypoxic tumor microenvironmentTumor perfusionSolid tumorsTherapeutic interventionsAnimal Models of COVID-19 II. Comparative Immunology
Veenhuis RT, Zeiss CJ. Animal Models of COVID-19 II. Comparative Immunology. ILAR Journal 2021, 62: ilab010-. PMID: 33914873, PMCID: PMC8135340, DOI: 10.1093/ilar/ilab010.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Animal modelsLarge animal modelCytokine surgeCell infiltrationAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionSevere coronavirus disease 2019SARS-CoV-2 infectionCoronavirus 2 infectionT cell responsesImmune cell infiltrationStrong antibody responseAnimal model studiesCoronavirus disease 2019Large animal model studyImmunological questionsHigh mortality rateCOVID-19Small animal modelsImmune system functionAfrican green monkeysSARS-CoV-2 researchVaccine efficacy
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