2025
Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Lopez J, Powles T, Braiteh F, Siu L, LoRusso P, Friedman C, Balmanoukian A, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher G, Schmidt M, Schuler M, Sullivan R, Burris H, Galvao V, Henick B, Dirix L, Jaeger D, Ott P, Wong K, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner R, Rittmeyer A, Laurie S, Gort E, Aljumaily R, Melero I, Sabado R, Rhee I, Mancuso M, Muller L, Fine G, Yadav M, Kim L, Leveque V, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao G, Low D, Petry C, Lo A, Schartner J, Delamarre L, Mellman I, Löwer M, Müller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lörks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kröner C, Tadmor A, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn A, Sahin U, Türeci Ö, Camidge D. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nature Medicine 2025, 31: 152-164. PMID: 39762422, PMCID: PMC11750724, DOI: 10.1038/s41591-024-03334-7.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAdvanced solid tumorsT cellsSolid tumorsCirculating CD8+ T cellsEfficacy of cancer immunotherapyTumor-infiltrating T cellsStimulate T cell responsesResponse to immunotherapyT cell responsesPreliminary antitumor activityPhase 1 studyPhase 1 trialDose escalationPretreated patientsCancer immunotherapyEvaluation of pharmacokineticsCD4+Tumor lesionsTreatment initiationTumor tissuesAtezolizumabClinical activityDisease characteristicsImmunotherapy
2024
Lactate fermentation intoxicates TILs
Hunt B, Kessler E, Joshi N. Lactate fermentation intoxicates TILs. Nature Immunology 2024, 25: 2176-2177. PMID: 39516647, DOI: 10.1038/s41590-024-02020-7.Peer-Reviewed Original ResearchTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarray
2023
Abstract B030: Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer
Jansen C, Vo B, Sobierajska E, Greenwald R, Mullane P, Prokhnevska N, Cardenas M, Bilen M, Osunkoya A, Master V, Kissick H. Abstract B030: Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer. Cancer Research 2023, 83: b030-b030. DOI: 10.1158/1538-7445.kidney23-b030.Peer-Reviewed Original ResearchTertiary lymphoid structuresSecondary lymphoid tissuesT cell responsesT cell zonesImmune nicheB cell zonesT cell nicheLymphoid tissueT cellsTumor tissuesEffective anti-tumor T cell responsesAnti-tumor T cell responsesDevelopment of T-cell functionStem-like CD8 T cellsImmune organsCD8 T cell activationCD8 T cell infiltrationTumor-infiltrating T cellsRobust T cell responsesCellular compositionB cell presenceHuman cancersAnti-tumor immunityResponse to immunotherapyCD8 T cellsBSBM-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
Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER).
Falchook G, Ribas A, Davar D, Eroglu Z, Wang J, Luke J, Hamilton E, Di Pace B, Wang T, Ghosh S, Dhar A, Borgovan T, Waszak A, LoRusso P. Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER). Journal Of Clinical Oncology 2022, 40: 2504-2504. DOI: 10.1200/jco.2022.40.16_suppl.2504.Peer-Reviewed Original ResearchTreatment-related treatment-emergent adverse eventsNon-small cell lung cancerPD-1 inhibitor nivolumabTreatment-emergent adverse eventsTumor-infiltrating T cellsPreliminary anti-tumor activityPhase 2 doseOpen-label studyPD-1 inhibitorsAdvanced solid tumorsPhase 2 studyDose-proportional mannerPhase 1 trialT cell suppressionCell lung cancerTherapeutic dose rangeMost common cancersAnti-tumor activityDose delaysPrior therapyInhibitor nivolumabPrimary endpointTim-3Adverse eventsPeritoneal mesotheliomaMultimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma
Leitner BP, Givechian KB, Ospanova S, Beisenbayeva A, Politi K, Perry RJ. Multimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma. Npj Precision Oncology 2022, 6: 8. PMID: 35087143, PMCID: PMC8795406, DOI: 10.1038/s41698-021-00248-2.Peer-Reviewed Original ResearchNon-small cell lung cancerLung squamous cell carcinomaBody mass indexSquamous cell carcinomaLung adenocarcinomaHigher glucose uptakeVisceral adiposityVisceral fatCell carcinomaLung cancerGlucose uptakeTreatment of NSCLCHigher body mass indexTumor-infiltrating T cellsImmune checkpoint inhibitionCell lung cancerHigh visceral fatPET/CT imagingTumors of patientsPrecision therapy approachesTumor glucose uptakePrecision medicine approachLUSC tumorsPrognostic gene expressionAdjunct therapy
2021
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies
Jansen JA, Omuro A, Lucca LE. T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies. Current Opinion In Neurology 2021, 34: 827-833. PMID: 34569985, PMCID: PMC8595795, DOI: 10.1097/wco.0000000000000988.Peer-Reviewed Original ResearchConceptsT cell dysfunctionTumor-infiltrating T cellsT cellsCell dysfunctionFuture immunotherapy strategiesCervical lymph nodesTumor-derived antigensImmune checkpoint blockadeCentral nervous systemHomeostatic brainSuccessful immunotherapyCheckpoint blockadeImmunotherapy strategiesLymph nodesTumor rejectionImmune surveillanceImmune responseMouse modelBrain tumorsLymphatic drainageNervous systemSolid tumorsDysfunctionSingle-cell RNA sequencingNatural historyCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2020
Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
Weiss SA, Zito C, Tran T, Heishima K, Neumeister V, McGuire J, Adeniran A, Kluger H, Jilaveanu LB. Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases. Journal Of Neuro-Oncology 2020, 152: 15-25. PMID: 32974852, PMCID: PMC7910371, DOI: 10.1007/s11060-020-03619-0.Peer-Reviewed Original ResearchConceptsT-cell contentMelanoma brain metastasesPD-L1 expressionLower microvessel densityMicrovessel densityBrain metastasesExtracranial metastasesMacrophage contentB cellsProspective therapeutic clinical trialsTumor-infiltrating T cellsImmune-modulating drugsImmune cell subsetsTherapeutic clinical trialsExtracerebral metastasesHigh CD68Low CD3Low CD8Systemic therapyIntracerebral metastasesMetastatic sitesCell subsetsMetastatic melanomaImmune cellsClinical trialsSubtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
Robinson MH, Vasquez J, Kaushal A, MacDonald TJ, Vega J, Schniederjan M, Dhodapkar K. Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma. Journal For ImmunoTherapy Of Cancer 2020, 8: e001066. PMID: 32788236, PMCID: PMC7422651, DOI: 10.1136/jitc-2020-001066.Peer-Reviewed Original ResearchConceptsT cell infiltrationHigh-grade gliomasT-cell densityLow-grade tumorsT cellsGlial tumorsTissue-resident memory T cellsTumor-resident T cellsPediatric gliomasTumor-infiltrating T cellsMemory T cellsCancer-related mortalityPediatric glial tumorsSingle-cell mass cytometryExpression of SOX2Stem cell markersImmune controlImmune therapyRecurrent tumorsImmune cellsImmunofluorescence immunohistochemistryPleomorphic xanthoastrocytomaBrain tumorsImmune architectureAdult gliomasDifferential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiformeTargeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease
Kemeny HR, Elsamadicy AA, Farber SH, Champion CD, Lorrey SJ, Chongsathidkiet P, Woroniecka KI, Cui X, Shen SH, Rhodin KE, Tsvankin V, Everitt J, Sanchez-Perez L, Healy P, McLendon RE, Codd PJ, Dunn IF, Fecci PE. Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease. Clinical Cancer Research 2020, 26: 1141-1151. PMID: 31744830, PMCID: PMC7809696, DOI: 10.1158/1078-0432.ccr-18-3486.Peer-Reviewed Original ResearchConceptsCushing's diseasePituitary adenomasPD-L1PD1/PD-L1 axisAdrenocorticotropic hormone plasma levelsTumor-infiltrating T cellsRefractory Cushing's diseasePD-L1 axisPD-L1 expressionCheckpoint blockade therapyNovel therapeutic optionsHormone plasma levelsElevated cortisol levelsLymphocytic hypophysitisAntitumor immunityBlockade therapyCheckpoint blockadeCheckpoint expressionNumerous sequelaeSignificant morbidityTherapeutic optionsPlasma levelsPreclinical modelsT cellsSuccessful therapy
2019
Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumors
2017
SOX2 immunity and tissue resident memory in children and young adults with glioma
Vasquez JC, Huttner A, Zhang L, Marks A, Chan A, Baehring JM, Kahle KT, Dhodapkar KM. SOX2 immunity and tissue resident memory in children and young adults with glioma. Journal Of Neuro-Oncology 2017, 134: 41-53. PMID: 28620836, PMCID: PMC7906294, DOI: 10.1007/s11060-017-2515-8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAntigen-Presenting CellsB7-H1 AntigenBrain NeoplasmsCell ProliferationChildChild, PreschoolCytokinesFemaleFlow CytometryGliomaHumansInfantMaleMyeloid CellsProgrammed Cell Death 1 ReceptorReceptors, ImmunologicRNA, Small InterferingSOXB1 Transcription FactorsT-LymphocytesTransfectionYoung AdultConceptsPediatric glial tumorsGlial tumorsT cellsExpression of SOX2Inhibitory checkpointsCD8/CD4 T cellsTissue-resident memory phenotypeTumor-infiltrating immune cellsTumor-infiltrating T cellsTumor cellsYoung adultsResident memory phenotypeTissue-resident memoryAnti-tumor immunityT cell immunityCD4 T cellsNatural killer cellsGlial tumor cellsNew antigenic targetsSingle-cell mass cytometryHigh mutation burdenStem cell antigenGlioma initiating cellsImmune checkpointsPD-1SOX2 as a target for immunotherapy of pediatric gliomas.
Vasquez J, Huttner A, Zhang L, Marks A, Chan A, Baehring J, Kahle K, Dhodapkar K. SOX2 as a target for immunotherapy of pediatric gliomas. Journal Of Clinical Oncology 2017, 35: e22012-e22012. DOI: 10.1200/jco.2017.35.15_suppl.e22012.Peer-Reviewed Original ResearchTumor-infiltrating T cellsImmune checkpoint blockadeT cellsPediatric glial tumorsGlial tumorsExpression of SOX2Inhibitory checkpointsCheckpoint blockadeTumor immunityGrade gliomasTissue-resident memory phenotypePediatric gliomasTumor-infiltrating immune cellsTumor cellsResident memory phenotypeT-cell proliferation assaysImmune checkpoint inhibitorsDendritic cell vaccinesPD-1 expressionSubset of CD4Anti-tumor immunityCD8 T cellsT cell immunityEffective tumor immunityPediatric brain tumorsSingle-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy.
Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Fan R, Halaban R, Zhou J. Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy. Journal Of Clinical Oncology 2017, 35: 49-49. DOI: 10.1200/jco.2017.35.7_suppl.49.Peer-Reviewed Original ResearchTumor-infiltrating T lymphocytesAnti-PD-1 therapyClinical outcomesCytokine profilingAnti-tumor T cell functionAnti-tumor T cell immunityTumor-infiltrating T cellsMIP-1 αAnti-tumor immunityT cell immunityResponse of patientsT cell functionCell immunityCheckpoint immunotherapyMelanoma patientsIL-8Metastatic melanomaCancer patientsTIL functionTIL analysisPatient responseT cellsT lymphocytesGranzyme BImmune function
2015
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses
Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, Kleinstein SH, Abel ED, Insogna KL, Feske S, Locasale JW, Bosenberg MW, Rathmell JC, Kaech SM. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Cell 2015, 162: 1217-1228. PMID: 26321681, PMCID: PMC4567953, DOI: 10.1016/j.cell.2015.08.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCD4-Positive T-LymphocytesEndoplasmic ReticulumGlycolysisHexokinaseImmunotherapyLymphocytes, Tumor-InfiltratingMelanomaMiceMonitoring, ImmunologicNFATC Transcription FactorsPhosphoenolpyruvateReceptors, Antigen, T-CellSarcoplasmic Reticulum Calcium-Transporting ATPasesSignal TransductionTransforming Growth Factor betaTumor MicroenvironmentConceptsAnti-tumor T cell responsesT cell responsesT cellsEffector functionsCell responsesTumor-reactive T cellsTumor-infiltrating T cellsPhosphoenolpyruvate carboxykinase 1Tumoricidal effector functionsTumor-specific CD4CD8 T cellsT cell activityMelanoma-bearing miceAerobic glycolysisActivated T cellsMetabolic checkpointTumor growthCell activityTumor microenvironmentNFAT SignalingMetabolic reprogrammingCarboxykinase 1Anabolic metabolismCellsATPase activity
2000
CD95 ligand expression as a mechanism of immune escape in breast cancer
Müschen M, Moers C, Warskulat U, Even J, Niederacher D, Beckmann M. CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 2000, 99: 69-77. PMID: 10651943, PMCID: PMC2327134, DOI: 10.1046/j.1365-2567.2000.00921.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBreast NeoplasmsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFas Ligand Proteinfas ReceptorFemaleFlow CytometryHumansImmunohistochemistryJurkat CellsLymphocyte CountMembrane GlycoproteinsProtein IsoformsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsBreast cancer cellsT cellsBreast cancerCD95L expressionImmune escapeIFN-gammaCancer cellsJurkat T cellsTumor-infiltrating T cellsCD95L mRNA levelsDepletion of CD4Cultured breast cancer cellsBreast cancer patientsPeripheral blood lymphocytesCD95/CD95L systemBreast cancer cell linesNon-malignant mammary tissuesActivated T cellsCD95 ligand expressionRate of apoptosisBreast cancer sectionsCancer cell linesInteraction of CD95Systemic immunosuppressionCancer patients
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