2025
T cell exhaustion: early or late in tumour progression?
Galluzzi L. T cell exhaustion: early or late in tumour progression? Nature Reviews Immunology 2025, 1-2. PMID: 40038448, DOI: 10.1038/s41577-025-01158-1.Peer-Reviewed Original ResearchKLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection
Fagerberg E, Attanasio J, Dien C, Singh J, Kessler E, Abdullah L, Shen J, Hunt B, Connolly K, De Brouwer E, He J, Iyer N, Buck J, Borr E, Damo M, Foster G, Giles J, Huang Y, Tsang J, Krishnaswamy S, Cui W, Joshi N. KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection. Science 2025, 387: eadn2337. PMID: 39946463, DOI: 10.1126/science.adn2337.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsCD8 T cell exhaustionNaive CD8 T cellsAcute LCMV infectionT cell exhaustionT cell fate decisionsLineage fidelityLCMV infectionEffector differentiationAcute infectionExhaustion programTranscription factorsImmune responseEpigenetic modulationSuppress differentiationProgenitor stateKLF2InfectionFunctional stateFate decisionsCD8Mitochondrial succinate feeds T cell exhaustion in cancer
Galluzzi L, Guilbaud E, Garg A. Mitochondrial succinate feeds T cell exhaustion in cancer. Cancer Cell 2025, 43: 168-170. PMID: 39933894, DOI: 10.1016/j.ccell.2025.01.005.Peer-Reviewed Original ResearchDiverse stromal phenotypes at spatial resolution in colorectal cancer peritoneal metastasis.
Zhao J, Ong J, Liu Y, Srivastava S, Teo M, Lee J, Walsh R, Loo L, Tan Q, Ng G, Tan J, Ma H, Ong X, Tay S, Sheng T, Lum J, Yong W, Pietrantonio F, Tan P, Sundar R. Diverse stromal phenotypes at spatial resolution in colorectal cancer peritoneal metastasis. Journal Of Clinical Oncology 2025, 43: 218-218. DOI: 10.1200/jco.2025.43.4_suppl.218.Peer-Reviewed Original ResearchCancer-associated fibroblastsT cell exhaustionPeritoneal metastasisT cellsStromal phenotypeColorectal cancerTissue microarrayStromal compartmentPoor prognosisSpatial distribution of T cellsColorectal cancer peritoneal metastasesIncreased CAFsClusters of T cellsCRC PMDistribution of T cellsTumor stroma compartmentAssociated with poor prognosisMemory B cellsDigital spatial profilingTranscoelomic disseminationTumor compartmentsStromal clustersPrognostic significanceTNF-alphaB cells
2024
Circulating Biomarkers and CD8+ T-Cell Subpopulations Reveal Evolving Phases of Immune Response in Patients Receiving Mosunetuzumab for Previously Untreated B-Cell Lymphoma
Milrod C, Chorzalska A, Morgan J, Pardo M, Raker C, Ollila T, Lee S, Pelcovits A, Reagan J, McMahon J, Donnelly S, Carmody C, Margolis J, Matasar M, Huntington S, Dubielecka P, Olszewski A. Circulating Biomarkers and CD8+ T-Cell Subpopulations Reveal Evolving Phases of Immune Response in Patients Receiving Mosunetuzumab for Previously Untreated B-Cell Lymphoma. Blood 2024, 144: 1614-1614. DOI: 10.1182/blood-2024-193023.Peer-Reviewed Original ResearchCD8+ T cellsCD8+ T cell subsetsT cell activationEM CD8+ T cellsB-cell lymphomaT cell subsetsT cellsBsAb therapyComplete responseEffector memoryImmune responseCD8+ T cell activationT cell-engaging therapiesTreatment of B-cell lymphomaCentral memory T cellsT cell activation markersAlternative administration schedulesCD8+T cell activityLow-dose lenalidomidePrior chemotherapy exposureMarginal zone lymphomaT cell exhaustionT-cell engagersAnti-lymphoma activityMemory T cellsProgestogen-driven B7-H4 contributes to onco-fetal immune tolerance
Yu J, Yan Y, Li S, Xu Y, Parolia A, Rizvi S, Wang W, Zhai Y, Xiao R, Li X, Liao P, Zhou J, Okla K, Lin H, Lin X, Grove S, Wei S, Vatan L, Hu J, Szumilo J, Kotarski J, Freeman Z, Skala S, Wicha M, Cho K, Chinnaiyan A, Schon S, Wen F, Kryczek I, Wang S, Chen L, Zou W. Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance. Cell 2024, 187: 4713-4732.e19. PMID: 38968937, PMCID: PMC11344674, DOI: 10.1016/j.cell.2024.06.012.Peer-Reviewed Original ResearchB7-H4Immune toleranceProgesterone receptorCD8<sup>+</sup> T cell exhaustionImmune tolerance checkpointB7-H4 expressionT cell exhaustionImmune tolerance mechanismsMaternal-fetal interfaceBreast cancer modelFemale sex hormonesBreast cancer progressionBreast cancer cellsTolerance checkpointsFetal resorptionHuman cancer typesHormonal screeningImmune activationPregnancy modelCancer modelsSex hormonesCell exhaustionPR antagonistsGenetic deficiencyCancer cellsAFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of responseReshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes
lledo delgado A, Preston-Hurlburt P, Currie S, Clark P, Herold K. Reshaping immune cells and the antigen-specific repertoire by anti-CD3 mAb teplizumab in Type 1 diabetes. The Journal Of Immunology 2024, 212: 0958_5059-0958_5059. DOI: 10.4049/jimmunol.212.supp.0958.5059.Peer-Reviewed Original ResearchCD8+ T cellsT cellsType 1 diabetesCD8+ T cell exhaustionAutoreactive CD8+ T cellsT cell exhaustionT cell changesCD8+ cellsProgression of type 1 diabetesAnti-CD3 mAbAntigen-specific repertoireAt-risk patientsCD8+CD4+Eomes expressionPeripheral bloodTeplizumabImmune cellsImmune regulationT1D diagnosisCD8Operational toleranceDelay progressionMonthsIndividuals at-riskClinical outcomes and immunological response to SARS-CoV-2 infection among people living with HIV
Amegashie E, Asamoah P, Ativi L, Adusei-Poku M, Bonney E, Tagoe E, Paintsil E, Torpey K, Quaye O. Clinical outcomes and immunological response to SARS-CoV-2 infection among people living with HIV. Experimental Biology And Medicine 2024, 249: 10059. PMID: 38628843, PMCID: PMC11020089, DOI: 10.3389/ebm.2024.10059.Peer-Reviewed Original ResearchConceptsLevels of inflammatory markersResponse to SARS-CoV-2 infectionClinical outcomesSARS-CoV-2 infectionCo-infectionInflammatory markersSARS-CoV-2HIV patients co-infectedImmune response to SARS-CoV-2 infectionCD4<sup>+</sup> countInitiation of ARTT cell exhaustionPatients co-infectedSevere outcomesAssociated with severe outcomesStudy assessed risk factorsMono-infected individualsResponse to SARS-CoV-2Respiratory tract infectionsImmunological response to SARS-CoV-2Immunological response to SARS-CoV-2 infectionAfrican American raceChronic kidney diseaseIntensive care unitPositive conversion rateBeyond T cell exhaustion: TIM-3 regulation of myeloid cells
Dixon K, Lahore G, Kuchroo V. Beyond T cell exhaustion: TIM-3 regulation of myeloid cells. Science Immunology 2024, 9: eadf2223. PMID: 38457514, DOI: 10.1126/sciimmunol.adf2223.Peer-Reviewed Original ResearchConceptsT cell exhaustionTim-3CD8<sup>+</sup> T cellsImmune responseRegulation of myeloid cell functionT cell stemnessTim-3 regulationImmune checkpoint moleculesT cell immunoglobulinCell-extrinsic mechanismsMyeloid cell functionRegulation of myeloid cellsCheckpoint moleculesTreatment of cancerCD4<sup>+</sup>T cellsMyeloid cellsCell-intrinsicCell functionAutoimmunityAutoinflammationCancerImmunoglobulinThiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma
Zhang X, Gao Y, Tang K, Li Z, Halberstam A, Zhou L, Perry R. Thiazolidinedione enhances the efficacy of anti-PD-1 monoclonal antibody in murine melanoma. AJP Endocrinology And Metabolism 2024, 326: e341-e350. PMID: 38294697, PMCID: PMC11901343, DOI: 10.1152/ajpendo.00346.2023.Peer-Reviewed Original ResearchPD-1 expressionCD8+ T cellsT cell exhaustionPD-1T cellsImmunotherapy efficacyAnti-programmed cell death protein 1Tumor-infiltrating CD8+ T cellsAnti-PD-1 monoclonal antibodyAnti-PD-1 responseAnti-PD-1 treatmentCell death protein 1Enhance immunotherapy efficacyEnhance immunotherapy responseImprove immunotherapy efficacyEfficacy of immunotherapyMurine melanoma modelTumor-bearing miceExpression of peroxisome proliferator-activated receptor gammaOverall survival timePeroxisome proliferator-activated receptor gammaEffect of obesityProliferator-activated receptor gammaHuman T cellsTreated in vitro
2023
Alterations in Immune Cell Composition during First-Line Therapy with Mosunetuzumab for Follicular or Marginal Zone Lymphoma
Olszewski A, Ollila T, Pelcovits A, Chorzalska A, Morgan J, McMahon J, Donnelly S, Huntington S, Matasar M, Reagan J, Milrod C, Dubielecka P. Alterations in Immune Cell Composition during First-Line Therapy with Mosunetuzumab for Follicular or Marginal Zone Lymphoma. Blood 2023, 142: 1651. DOI: 10.1182/blood-2023-181418.Peer-Reviewed Original ResearchEnd of therapyCytokine release syndromeMarginal zone lymphomaT cellsComplete responsePD1 expressionNK cellsB cellsEffector memory T cellsCheckpoint inhibitor combinationsExpression of LAG3Immune cell changesB-cell depletionFirst-line therapyExpansion of TregsT cell exhaustionMemory T cellsPrior chemotherapy exposureImmune cell subsetsImmune cell compositionPeripheral blood samplesMulticolor flow cytometrySignificant increaseTreatment-induced changesExhausted phenotypePrediction Modeling of CAR-T Cell Therapy for Diffuse Large B-Cell Lymphoma Using Artificial Neural Networks on Tumor Vascular Phenotype
Verma A, Liburd S, Tobias Z, Isufi I, Pober J, Xu M. Prediction Modeling of CAR-T Cell Therapy for Diffuse Large B-Cell Lymphoma Using Artificial Neural Networks on Tumor Vascular Phenotype. Blood 2023, 142: 2075. DOI: 10.1182/blood-2023-184963.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaPre-treatment biopsiesVenular endothelial cellsLarge B-cell lymphomaMemory T cellsHigh endothelial venulesT cellsB-cell lymphomaVCAM-1E-selectinICAM-1Endothelial cellsChimeric antigen receptor T-cell therapyL-selectinPre-treatment tumor biopsiesEffector memory T cellsCentral memory T cellsCAR T-cell therapyCell therapyHEV endothelial cellsInflamed lymph nodesT-cell infiltratesT cell exhaustionT-cell therapyT-cell homingThe 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 functionCancer- and infection-induced T cell exhaustion are distinct
Buck J, Joshi N. Cancer- and infection-induced T cell exhaustion are distinct. Nature Immunology 2023, 24: 1604-1605. PMID: 37709988, DOI: 10.1038/s41590-023-01624-9.Peer-Reviewed Original ResearchCancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence
Chen J, Madina B, Ahmadi E, Yarovinsky T, Krady M, Meehan E, Wang I, Ye X, Pitmon E, Ma X, Almassian B, Nakaar V, Wang K. Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence. Acta Pharmaceutica Sinica B 2023, 14: 335-349. PMID: 38261838, PMCID: PMC10792965, DOI: 10.1016/j.apsb.2023.08.034.Peer-Reviewed Original ResearchCancer immunotherapyTumor recurrenceShort hairpin RNASurvival benefitIL-12Immune mechanismsLong-term survival benefitIL-17 receptor ACancer-promoting inflammationLarge established tumorsMultiple immune mechanismsPD-L1 pathwayT cell exhaustionDeath ligand 1Human cancer immunotherapySelf-amplifying mRNATumor-bearing miceVirus-like vesiclesMechanism of protectionCombined immunomodulationContralateral tumorsIL-17Established tumorsAbscopal effectImmunological memoryDynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma
Lu L, Risch E, Halaban R, Zhen P, Bacchiocchi A, Risch H. Dynamic changes of circulating soluble PD-1/PD-L1 and its association with patient survival in immune checkpoint blockade-treated melanoma. International Immunopharmacology 2023, 118: 110092. PMID: 37004344, DOI: 10.1016/j.intimp.2023.110092.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeSoluble PD-L1 (sPD-L1) levelsPD-L1 ratioPD-L1 levelsSoluble PD-1Soluble PD-L1PD-L1PD-1Patient survivalSurvival statusPD-1/PD-L1Immune checkpoints PD-1T cell exhaustionPatients' survival statusSolid tumor typesInitial immunotherapyCheckpoint blockadeMelanoma patientsPoor prognosisRetrospective studyPatient responseCell exhaustionTumor typesMelanomaSurvival
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 immunogenicityTherapyCancer
2021
Tumour antigen-induced T cell exhaustion — the archenemy of immune-hot malignancies
Lopez de Rodas M, Schalper KA. Tumour antigen-induced T cell exhaustion — the archenemy of immune-hot malignancies. Nature Reviews Clinical Oncology 2021, 18: 749-750. PMID: 34556846, PMCID: PMC9235859, DOI: 10.1038/s41571-021-00562-5.Peer-Reviewed Original ResearchConceptsT cell exhaustionCell exhaustionTumor antigen-specific effector T cellsAntigen-specific effector T cellsTissue-resident memory phenotypeT-cell alterationsEffector T cellsCell-specific antigensMemory phenotypeLung carcinomaClinical significanceT cellsHuman melanomaTumor microenvironmentCell alterationsSingle-cell strategyRecent studiesCD8CarcinomaMalignancyMelanomaExhaustionAntigenImpact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival
Li W, Amei A, Bui F, Norouzifar S, Lu L, Wang Z. Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival. Cancers 2021, 13: 2879. PMID: 34207556, PMCID: PMC8228363, DOI: 10.3390/cancers13122879.Peer-Reviewed Original ResearchT cell activationNeoantigen expressionChi-squared testOverall survivalBreast cancerMultivariable Cox proportional hazards modelsMultivariable Cox regression modelsCox proportional hazards modelImproved overall survivalT-cell statusT cell exhaustionBreast cancer patientsKaplan-Meier survivalBreast cancer survivalCox regression modelClinical-pathological variablesReceptor-positive subgroupCancer immunotherapy efficacyProportional hazards modelPearson's chi-squared testTumor-specific somatic mutationsSpearman correlation analysisImmunotherapy efficacyPathological variablesPatient survival
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