2025
Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisition
2024
Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer
Campbell M, Wolf D, Yau C, Brown-Swigart L, Wulfkuhle J, Gallagher I, Zhu Z, Bolen J, Vandenberg S, Hoyt C, Mori H, Borowsky A, Sit L, Perlmutter J, Asare S, Investigators I, Nanda R, Liu M, Yee D, DeMichele A, Hylton N, Pusztai L, Berry D, Hirst G, Petricoin E, Veer L, Esserman L. Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer. Cell Reports Medicine 2024, 5: 101799. PMID: 39510069, PMCID: PMC11604542, DOI: 10.1016/j.xcrm.2024.101799.Peer-Reviewed Original ResearchImmune checkpoint blockadeI-SPY 2 TRIALPathological complete responseTumor microenvironmentBreast cancerAssociated with pathologic complete responseBreast cancer receptor subtypesNeoadjuvant immune checkpoint blockadePD-L1<sup>+</sup> cellsSpatial distribution of immune cellsDistribution of immune cellsEarly-stage breast cancerImmune checkpoint inhibitorsBiomarkers of responseImmune cell populationsImmune cell densityAssociated with responseImmune cell signalingCheckpoint blockadeCheckpoint inhibitorsComplete responsePretreatment biopsiesReceptor subtypesT cellsImmune cellsTargeted Dynamic Phospho-Proteogenomic Analysis of Gastric Cancer Cells Suggests Host Immunity Provides Survival Benefit
Kume K, Iida M, Iwaya T, Yashima-Abo A, Koizumi Y, Endo A, Wade K, Hiraki H, Calvert V, Wulfkuhle J, Espina V, Siwak D, Lu Y, Takemoto K, Suzuki Y, Sasaki Y, Tokino T, Petricoin E, Liotta L, Mills G, Nishizuka S. Targeted Dynamic Phospho-Proteogenomic Analysis of Gastric Cancer Cells Suggests Host Immunity Provides Survival Benefit. Molecular & Cellular Proteomics 2024, 23: 100870. PMID: 39461475, PMCID: PMC11621936, DOI: 10.1016/j.mcpro.2024.100870.Peer-Reviewed Original ResearchDNA-damaging drugsTotal lymphocyte countCell linesResistance to DNA damaging drugsPD-L1Adjuvant chemotherapyProtein dynamicsProtein-level regulationSurvival benefitCopy number lossExpression time courseGastric cancerRelapse-free survival rateGastric cancer cellsHost immunityAssociated with prolonged survivalIncreased STAT1 phosphorylationResistance to other drugsGlobal protein dynamicsImmune checkpoint blockadePD-L1 positivityPD-L1 expressionAdvanced gastric cancerExpression of STAT1Molecular targeted drugsCTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockadePeripheral blood cytokines and outcomes with immune checkpoint blockade: a systematic review and meta-analysis
Karol A, Fujiwara Y, D'Ovidio T, Baldwin E, Joshi H, Doroshow D, Galsky M. Peripheral blood cytokines and outcomes with immune checkpoint blockade: a systematic review and meta-analysis. Immunotherapy 2024, 16: 829-840. PMID: 39155854, PMCID: PMC11457654, DOI: 10.1080/1750743x.2024.2379230.Peer-Reviewed Original ResearchImmune checkpoint blockadeProgression-free survivalC-reactive proteinPeripheral blood cytokinesOverall survivalTumor-promoting inflammationCheckpoint blockadeInterleukin-6Interleukin-8Blood cytokinesOn-treatment declineIL-8 levelsTrial end pointsIL-6 levelsPharmacodynamic biomarkersInflammatory cytokinesEnd pointsResponse rateCytokinesMeta-analysisSystematic reviewBlockadeInflammationORRSurvivalUltra-sensitive ctDNA dynamics to capture therapy response in pembrolizumab-treated gastroesophageal cancer.
Nixon A, Navarro F, Zhou K, Abbott C, Howard L, Brady J, Liu Y, Jia J, Niedzwiecki D, Chen R, Strickler J, Boyle S, Uronis H. Ultra-sensitive ctDNA dynamics to capture therapy response in pembrolizumab-treated gastroesophageal cancer. Journal Of Clinical Oncology 2024, 42: 4025-4025. DOI: 10.1200/jco.2024.42.16_suppl.4025.Peer-Reviewed Original ResearchMetastatic esophagogastric cancerMolecular residual diseaseImmune checkpoint blockadeProgression-free survivalCtDNA dynamicsCtDNA levelsHigher hazard ratioOverall survivalDetection of molecular residual diseasePhase II study of pembrolizumabSingle-arm phase II studyWhole-genome sequencingSingle nucleotide variantsMolecular progressionResponse rateStudy of pembrolizumabBaseline prior to treatmentUnivariate Cox regression analysisCox regression analysisFFPE tumor samplesOverall response rateMedian lead timeImprove treatment decision-makingLong-term survivalLiquid biopsy platformMolecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Zaemes J, Hugaboom M, Shah V, Haas N, McDermott D, Jegede O, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Hurwitz M, Wu C, Einstein D, Hammers H, Signoretti S, West D, Denize T, Atkins M, Braun D. Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC). Journal Of Clinical Oncology 2024, 42: 4546-4546. DOI: 10.1200/jco.2024.42.16_suppl.4546.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint blockadeProgression-free survivalProgressive diseaseAnti-VEGFOverall survivalAssociated with higher progression-free survivalTumor samplesAdvanced clear cell renal cell carcinomaCombined immune checkpoint blockadeHigher progression-free survivalIncreased PFSImmune checkpoint blockade therapyShorter progression-free survivalClear cell renal cell carcinomaAnti-VEGF therapyCell renal cell carcinomaWeeks of therapyRenal cell carcinomaBiomarkers of efficacyFFPE tumor samplesNIVO monotherapyCheckpoint blockadeDecreased OSProspective trialsARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity
Maxwell M, Hom-Tedla M, Yi J, Li S, Rivera S, Yu J, Burns M, McRae H, Stevenson B, Coakley K, Ho J, Gastelum K, Bell J, Jones A, Eskander R, Dykhuizen E, Shadel G, Kaech S, Hargreaves D. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 2024, 187: 3390-3408.e19. PMID: 38754421, PMCID: PMC11193641, DOI: 10.1016/j.cell.2024.04.025.Peer-Reviewed Original ResearchImmune checkpoint blockadeAnti-tumor immunityIncreased CD8+ T cell infiltrationCD8+ T cell infiltrationT cell infiltrationType I IFN signalingGene expression signaturesICB treatmentCheckpoint blockadeIndependent of microsatellite instabilityARID1A mutationsCytolytic activityImmune phenotypeMurine modelCell infiltrationARID1A lossClinical trialsMutant cancersARID1AHuman cancersExpression signaturesGene upregulationMicrosatellite instabilityCancerInterferonSingle-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer
Wang L, Izadmehr S, Sfakianos J, Tran M, Beaumont K, Brody R, Cordon-Cardo C, Horowitz A, Sebra R, Oh W, Bhardwaj N, Galsky M, Zhu J. Single-cell transcriptomic-informed deconvolution of bulk data identifies immune checkpoint blockade resistance in urothelial cancer. IScience 2024, 27: 109928. PMID: 38812546, PMCID: PMC11133924, DOI: 10.1016/j.isci.2024.109928.Peer-Reviewed Original ResearchScRNA-seqTumor microenvironmentUrothelial cancerRNA sequencingRNA-seq datasetsRNA-seq dataSingle-cellSingle-cell RNA sequencingMinor cell typesCohorts treated with immune checkpoint inhibitorsResistance to immune checkpoint blockadeImmune checkpoint blockade resistanceCheckpoint blockade resistanceImmune checkpoint blockadeImmune checkpoint inhibitorsTumor microenvironment heterogeneityFeatures associated with poor outcomeSpatial genomicsHuman urothelial cancerInfluence tumor progressionClinically relevant insightsCheckpoint blockadeCheckpoint inhibitorsTreatment responseCell typesMIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy
Fey R, Nichols R, Tran T, Vandenbark A, Kulkarni R. MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy. Cancers 2024, 16: 1773. PMID: 38730725, PMCID: PMC11082995, DOI: 10.3390/cancers16091773.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune-related adverse events developmentResponse to ICB therapyImmune checkpoint blockade therapyImmune checkpoint blockadePredictive biomarkersICB therapyCheckpoint blockade therapySerum MIF levelsBlockade therapyCheckpoint blockadeMIF levelsMalignant melanomaTreatment resistanceSolid tumorsAdverse eventsAutoimmune diseasesContext of cancerPrognostic biomarkerCancer progressionCognate receptor CD74Receptor CD74TherapyCD74CancerTherapeutic Targeting of DNA Repair Pathways in Pediatric Extracranial Solid Tumors: Current State and Implications for Immunotherapy
Zhao S, Prior D, Heske C, Vasquez J. Therapeutic Targeting of DNA Repair Pathways in Pediatric Extracranial Solid Tumors: Current State and Implications for Immunotherapy. Cancers 2024, 16: 1648. PMID: 38730598, PMCID: PMC11083679, DOI: 10.3390/cancers16091648.Peer-Reviewed Original ResearchDNA damage repair inhibitorsPediatric extracranial solid tumorDNA damage repair deficiencyExtracranial solid tumorSolid tumorsDNA damage repairResponse to immune checkpoint blockadeCombinations of DDR inhibitorsEnhance tumor immunogenicityImmune checkpoint blockadePediatric solid tumorsTherapeutic targetPediatric clinical trialsDNA damage repair pathwaysDDR pathwaysCheckpoint blockadeTumor immunogenicityDNA damagePediatric tumorsPotential therapeutic targetDDR inhibitorsClinical trialsTumorHuman cancersRepair DNA damageC-reactive protein (CRP) as a prognostic biomarker in patients with urothelial carcinoma: A systematic review and meta-analysis
Fujiwara Y, Karol A, Joshi H, Reford E, Izadmehr S, Doroshow D, Galsky M. C-reactive protein (CRP) as a prognostic biomarker in patients with urothelial carcinoma: A systematic review and meta-analysis. Critical Reviews In Oncology/Hematology 2024, 197: 104352. PMID: 38614269, PMCID: PMC11219184, DOI: 10.1016/j.critrevonc.2024.104352.Peer-Reviewed Original ResearchConceptsProgression-free survivalC-reactive proteinUrothelial carcinomaTumor-promoting inflammationOverall survivalCRP valuesHazard ratioPro-inflammatory tumor microenvironmentAssociated with shorter OSICB-treated patientsImmune checkpoint blockadeEvaluate survival outcomesRandom-effects model meta-analysesHigher CRP levelsSystematic reviewMeta-analysesLow CRP valuesCheckpoint blockadeShorter OSSurvival outcomesTumor microenvironmentCRP levelsPrognostic biomarkerCarcinomaPatientsDetection of sarcomatoid renal cell carcinoma using plasma cell-free DNA methylation.
Semaan K, El Zarif T, Seo J, Eid M, Canniff J, Fortunato B, Savignano H, Davidsohn M, Lakshminarayanan G, Saad E, Saliby R, Bakouny Z, Matar S, Nuzzo P, Berchuck J, Signoretti S, Braun D, Freedman M, Baca S, Choueiri T. Detection of sarcomatoid renal cell carcinoma using plasma cell-free DNA methylation. Journal Of Clinical Oncology 2024, 42: 449-449. DOI: 10.1200/jco.2024.42.4_suppl.449.Peer-Reviewed Original ResearchDifferentially methylated regionsRenal cell carcinomaCell-free DNAMeDIP-seqSarcomatoid differentiationDNA methylation signalsArea under the receiver operating characteristicHigh-throughput sequencingCell carcinomaCell-free DNA methylationFalse discovery rateResponse to immune checkpoint blockadeEpigenomic approachesCfMeDIP-seqSarcomatoid renal cell carcinomaMethylation immunoprecipitationDNA methylationHistological subtypes of cancerAssociated with poor survivalImmune checkpoint blockadeSubtypes of cancerDana-Farber Cancer InstituteSpatial heterogeneityArea under the receiver operating characteristic curveWilcoxon rank sum testTargeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy
Alcantara M, Tang W, Wang D, Kaniowski D, Kang E, Dizman N, Chehrazi-Raffle A, Meza L, Zengin Z, Hall J, Hsu J, Egelston C, Moreira D, Horsager A, Pal S, Kortylewski M. Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy. Frontiers In Immunology 2024, 14: 1274781. PMID: 38259453, PMCID: PMC10800835, DOI: 10.3389/fimmu.2023.1274781.Peer-Reviewed Original ResearchImmune checkpoint blockadeDendritic cellsCancer patientsBladder cancerT cellsTumor-associated antigen-presenting cellsTherapeutic efficacyLesser extent IL-10T cell-based immunotherapyImmune checkpoint inhibitorsTumor immune evasionAntitumor immune responseCD8 T cellsRegulatory T cellsBladder cancer immunotherapyCell-based immunotherapyAntigen-presenting cellsSTAT3 activationRenal cancer patientsBladder cancer patientsImmune cell activityMyeloid immune cellsICB resistanceIpilimumab immunotherapyCheckpoint inhibitorsThe Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers
Mustafa S, Jansen C, Jani Y, Evans S, Zhuang T, Brown J, Nazha B, Master V, Bilen M. The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers. Biomarker Insights 2024, 19: 11772719241254179. PMID: 38827239, PMCID: PMC11143877, DOI: 10.1177/11772719241254179.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsResponse to immunotherapyAdverse eventsTreatment of genitourinary malignanciesImmune checkpoint blockadeSelection of therapySignificant side effectsCheckpoint blockadeCheckpoint inhibitorsGU malignanciesGenitourinary malignanciesPatient tumorsTreatment landscapeReview of biomarkersGenitourinary cancersGU tumorsPreclinical studiesPrognostic toolSide effectsTherapyBiomarker developmentTumorPatientsImmunotherapy
2023
An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis
LaMarche N, Hegde S, Park M, Maier B, Troncoso L, Le Berichel J, Hamon P, Belabed M, Mattiuz R, Hennequin C, Chin T, Reid A, Reyes-Torres I, Nemeth E, Zhang R, Olson O, Doroshow D, Rohs N, Gomez J, Veluswamy R, Hall N, Venturini N, Ginhoux F, Liu Z, Buckup M, Figueiredo I, Roudko V, Miyake K, Karasuyama H, Gonzalez-Kozlova E, Gnjatic S, Passegué E, Kim-Schulze S, Brown B, Hirsch F, Kim B, Marron T, Merad M. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature 2023, 625: 166-174. PMID: 38057662, PMCID: PMC11189607, DOI: 10.1038/s41586-023-06797-9.Peer-Reviewed Original ResearchConceptsInterleukin-4IL-4RαMyeloid cellsCheckpoint blockadeTumor burdenPD-1/PD-L1 checkpoint blockadePD-1/PD-L1 blockadeBone marrowTumor-infiltrating CD8 T cellsType 2 cytokines interleukin-4PD-L1 checkpoint blockadeCell lung cancer lesionsNon-small cell lung cancer lesionsDepletion of basophilsPD-L1 blockadePrimary disease siteCD8 T cellsImmune checkpoint blockadeLung cancer lesionsNovel combination therapiesCytokine interleukin-4Bone marrow basophilsConditional knockout miceRefractory NSCLCEarly myeloid progenitorsThe tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer
Taifour T, Attalla S, Zuo D, Gu Y, Sanguin-Gendreau V, Proud H, Solymoss E, Bui T, Kuasne H, Papavasiliou V, Lee C, Kamle S, Siegel P, Elias J, Park M, Muller W. The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer. Immunity 2023, 56: 2755-2772.e8. PMID: 38039967, DOI: 10.1016/j.immuni.2023.11.002.Peer-Reviewed Original ResearchTriple-negative breast cancerImmune checkpoint blockadeBreast cancerAnti-tumor immune responseHuman triple-negative breast cancerNeutrophil extracellular trap formationT cell exclusionAnti-tumor immunityPoor clinical outcomeImmunosuppressive tumor microenvironmentMammary tumor onsetNeutrophil extracellular trapsExtracellular trap formationBreast cancer modelMurine breast tumorsClinical outcomesNeutrophil recruitmentCell infiltrationCHI3L1 expressionTumor infiltrationExtracellular trapsTranscription factor STAT3Immune responseLack of responsivenessSolid tumorsTargeting 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 optionsAntibacterial Fusobacterium nucleatum‐Mimicking Nanomedicine to Selectively Eliminate Tumor‐Colonized Bacteria and Enhance Immunotherapy Against Colorectal Cancer
Chen L, Zhao R, Shen J, Liu N, Zheng Z, Miao Y, Zhu J, Zhang L, Wang Y, Fang H, Zhou J, Li M, Yang Y, Liu Z, Chen Q. Antibacterial Fusobacterium nucleatum‐Mimicking Nanomedicine to Selectively Eliminate Tumor‐Colonized Bacteria and Enhance Immunotherapy Against Colorectal Cancer. Advanced Materials 2023, 35: e2306281. PMID: 37722134, DOI: 10.1002/adma.202306281.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeF. nucleatumTumor modelTherapeutic responseResponse to immune checkpoint blockadeColorectal cancerColorectal tumorsImmunosuppressive tumor microenvironmentColorectal cancer modelAnimal tumor modelsAgainst Colorectal CancerColorectal tumor cellsICB therapyCheckpoint blockadeCancer immunotherapyTumor microenvironmentFusobacterium nucleatumMC-38Cancer modelsTumor cellsClinical evidenceTumor developmentSide effectsTumorCancer treatmentThe β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell function
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