2025
Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer
Belabed M, Park M, Blouin C, Balan S, Moon C, Freed G, Quijada-Álamo M, Peros A, Mattiuz R, Reid A, Yatim N, Boumelha J, Azimi C, LaMarche N, Troncoso L, Amabile A, Le Berichel J, Chen S, Wilk C, Brown B, Radford K, Ghosh S, Rothlin C, Yvan-Charvet L, Marron T, Puleston D, Wagenblast E, Bhardwaj N, Lamaze C, Merad M. Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer. Nature Immunology 2025, 26: 188-199. PMID: 39838105, DOI: 10.1038/s41590-024-02065-8.Peer-Reviewed Original ResearchConventional dendritic cellsNiemann-Pick disease type C1Maturation of conventional dendritic cellsExpression of maturation markersCholesterol mobilizationAnti-tumor immunityReceptor tyrosine kinase AXLDendritic cell maturationResponse to cancerTyrosine kinase AXLDendritic cellsImmune receptor signalingMaturation markersAuto-immunityCell maturationReceptor signalingImmunogenic responseTherapeutic targetCholesterol transportLipid nanodomainsSubcellular mechanismsCholesterolType C1CancerCell surfaceTrogocytosis-mediated immune evasion in the tumor microenvironment
Kim J, Park S, Kim J, Kim Y, Yoon H, Rayhan B, Jeong J, Bothwell A, Shin J. Trogocytosis-mediated immune evasion in the tumor microenvironment. Experimental & Molecular Medicine 2025, 57: 1-12. PMID: 39741180, PMCID: PMC11799389, DOI: 10.1038/s12276-024-01364-2.Peer-Reviewed Original ResearchConceptsCD4 T cellsT cellsMajor histocompatibility complexTumor microenvironmentImmune evasionMechanisms of immune evasionAnti-tumor immunityImmune regulatory moleculesAntigen-presenting cellsImmune-regulatory moleculesCTLA-4Cell-to-cell interactionsDonor cellsHistocompatibility complexTrogocytosisRecipient cellsTumorMembrane lossMembrane moleculesRegulatory moleculesMicroenvironmentSurface localizationPlasma membraneCellsTrogoptosis
2024
Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma
Lu B, Lucca L, Lewis W, Wang J, Nogueira C, Heer S, Rayon-Estrada V, Axisa P, Reeves S, Buitrago-Pocasangre N, Pham G, Kojima M, Wei W, Aizenbud L, Bacchiocchi A, Zhang L, Walewski J, Chiang V, Olino K, Clune J, Halaban R, Kluger Y, Coyle A, Kisielow J, Obermair F, Kluger H, Hafler D. Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma. Nature Immunology 2024, 26: 82-91. PMID: 39609626, DOI: 10.1038/s41590-024-02023-4.Peer-Reviewed Original ResearchCD8+ T cellsAnti-tumor immunityRegulatory T cellsT cellsSubpopulation of CD8+ T cellsCytotoxic CD8+ T cellsHuman CD8+ T cellsTumor antigen-specific CD8Impaired anti-tumor immunityTumor antigen-specificPoor overall survivalTumor rejectionKIR expressionOverall survivalTumor antigensImmune evasionCellular mediatorsHuman cancersCD8MelanomaTumorTranscriptional programsFunctional heterogeneityImmunityPatientsThe analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably?
Vidal J, Tsiknakis N, Staaf J, Bosch A, Ehinger A, Nimeus E, Salgado R, Bai Y, Rimm D, Hartman J, Acs B. The analytical and clinical validity of AI algorithms to score TILs in TNBC: can we use different machine learning models interchangeably? EClinicalMedicine 2024, 78: 102928. PMID: 39634035, PMCID: PMC11615110, DOI: 10.1016/j.eclinm.2024.102928.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor-infiltrating lymphocytesBreast Cancer Research FoundationPrognostic validityMetastatic triple-negative breast cancerDisease-free survival endpointsHazard ratioHost anti-tumor immunityScored tumor infiltrating lymphocytesTumor-infiltrating lymphocyte scoresTriple-negative breast cancer patientsYears median follow-upTumour-infiltrating lymphocyte assessmentAnti-tumor immunityMedian follow-upIndependent prospective cohortTNBC tumorsPrognostic potentialProspective cohortBreast cancerPrognostic performanceAnalytic cohortFollow-upSchool of MedicineSwedish Society for Medical ResearchScavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling.
Xu Z, Kuhlmann-Hogan A, Xu S, Tseng H, Chen D, Tan S, Sun M, Tripple V, Bosenberg M, Miller-Jensen K, Kaech S. Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling. Cancer Research 2024, 85: 462-476. PMID: 39546763, PMCID: PMC11788022, DOI: 10.1158/0008-5472.can-23-4027.Peer-Reviewed Original ResearchTumor-associated macrophagesIFN-ITumor microenvironmentTumor growthHeterogeneous population of myeloid cellsPharmacological inhibition of CD36Population of myeloid cellsTumor cell quiescenceAnti-tumor immunityDelayed tumor growthTumor inflammatory microenvironmentElevated type I interferonReduced tumor growthMyeloid-specific deletionDeletion of CD36Type I interferon signalingInhibition of CD36Promote cancer progressionI interferon signalingIFN-I responseIFN-I signalingType I interferonScavenger receptor CD36TAM functionNatural suppressorTMED4 facilitates Treg suppressive function via ROS homeostasis in tumor and autoimmune mouse models
Jiang Z, Wang H, Wang X, Duo H, Tao Y, Li J, Li X, Liu J, Ni J, Wu E, Xiang H, Guan C, Wang X, Zhang K, Zhang P, Hou Z, Liu Y, Wang Z, Su B, Li B, Hao Y, Li B, Wu X. TMED4 facilitates Treg suppressive function via ROS homeostasis in tumor and autoimmune mouse models. Journal Of Clinical Investigation 2024, 135: e179874. PMID: 39480507, PMCID: PMC11684806, DOI: 10.1172/jci179874.Peer-Reviewed Original ResearchEndoplasmic reticulum stressER-associated degradationSuppressive functionTreg cellsFoxp3 stabilityReactive oxygen speciesSuppressive function of Treg cellsFunction of Treg cellsExacerbated inflammatory phenotypeAnti-tumor immunityTreg suppressive functionRegulatory T cellsTreg cell stabilityT cell hyperactivationAutoimmune mouse modelReactive oxygen species homeostasisTreg signatureT cellsTregsInflammatory phenotypeReactive oxygen species scavengingMouse modelTMED4Excessive reactive oxygen speciesProtein 4The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity
Nguyen N, Müller R, Briukhovetska D, Weber J, Feucht J, Künkele A, Hudecek M, Kobold S. The Spectrum of CAR Cellular Effectors: Modes of Action in Anti-Tumor Immunity. Cancers 2024, 16: 2608. PMID: 39061247, PMCID: PMC11274444, DOI: 10.3390/cancers16142608.Peer-Reviewed Original ResearchCAR-T cellsLimitations of CAR-T cellsChimeric antigen receptor T cellsBiology of solid tumorsAdoptive cell therapyAnti-tumor immunityCo-stimulatory domainTransgenic cytokinesHLA incompatibilityMode of actionNK cellsHLA compatibilitySwitch receptorsDendritic cellsTumor microenvironmentHematologic neoplasiaT cellsHematological tumorsSolid tumorsImmune cellsAntigen presentationCell therapyCAR activationCellular vehiclesResponse rateObesity induces PD-1 on macrophages to suppress anti-tumour immunity
Bader J, Wolf M, Lupica-Tondo G, Madden M, Reinfeld B, Arner E, Hathaway E, Steiner K, Needle G, Hatem Z, Landis M, Faneuff E, Blackman A, Wolf E, Cottam M, Ye X, Bates M, Smart K, Wang W, Pinheiro L, Christofides A, Smith D, Boussiotis V, Haake S, Beckermann K, Wellen K, Reinhart-King C, Serezani C, Lee C, Aubrey C, Chen H, Rathmell W, Hasty A, Rathmell J. Obesity induces PD-1 on macrophages to suppress anti-tumour immunity. Nature 2024, 630: 968-975. PMID: 38867043, PMCID: PMC11456854, DOI: 10.1038/s41586-024-07529-3.Peer-Reviewed Original ResearchTumor-associated macrophagesPD-1 expressionInduced PD-1 expressionPD-1T cellsIncreased CD8+ T cell activationCD8+ T cell activationResponse to immune checkpoint blockade therapyT-cell stimulatory potentialTumor-associated macrophage expressionSuppress anti-tumor immunityImmune checkpoint blockade therapyObesity-cancer connectionPD-1 deficiencyAnti-PD-1PD-1 blockadePD-1 inhibitionAnti-tumor immunityCheckpoint blockade therapyTargeting PD-1Tumor immune surveillancePD-1 immunotherapyAntigen presentation capabilityMarkers of exhaustionExpression of CD86Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling.
Saha S, Ghosh M, Li J, Wen A, Galluzzi L, Martinez L, Montrose D. Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling. Cancer Research 2024, 84: 2645-2659. PMID: 38861367, PMCID: PMC11326969, DOI: 10.1158/0008-5472.can-23-1788.Peer-Reviewed Original ResearchAnti-tumor immunityImmune checkpoint inhibitors targeting PD-1Improved response to immune checkpoint inhibitorsCheckpoint inhibitors targeting PD-1Infiltration of immune effector cellsSuppressors of anti-tumor immunityColorectal cancerResponse to immune checkpoint inhibitorsEnhance tumor immunogenicityI interferonImmune checkpoint inhibitorsT-cell depletionCancer metabolismSerine deprivationImmune effector cellsSensitivity of tumorsType I IFN signalingAnti-neoplastic effectsImmune-enhancing effectsDisrupted metabolic pathwaysColorectal cancer cellsType I interferonCheckpoint inhibitorsIntratumoral infiltrationPD-1DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism
Li S, Ouyang X, Sun H, Jin J, Chen Y, Li L, Wang Q, He Y, Wang J, Chen T, Zhong Q, Liang Y, Pierre P, Zou Q, Ye Y, Su B. DEPDC5 protects CD8+ T cells from ferroptosis by limiting mTORC1-mediated purine catabolism. Cell Discovery 2024, 10: 53. PMID: 38763950, PMCID: PMC11102918, DOI: 10.1038/s41421-024-00682-z.Peer-Reviewed Original ResearchCD8+ T cellsPeripheral CD8+ T cellsAnti-tumor immunityT cellsTumor-infiltrating CD8+ T cellsCD8+ T cell homeostasisCD8+ T cell numbersImpaired anti-tumor immunityT cell numbersT-cell protectionT cell homeostasisCancer patient survivalLevels of xanthine oxidasePatient survivalCD8Epilepsy patientsDEPDC5Suppression of ferroptosisMTORC1 signalingFerroptosisMolecular mechanismsImmunityXanthine oxidasePurine catabolismExpressionARID1A 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 instabilityCancerInterferonThe FLRT3-UNC5B Pathway is a Novel Regulator of T Immunosurveillance
Flies D, Yan C, Yang Q, Arbitman S, Fitzgerald D, Sharee S, Shaik J, Bosiacki J, Myers K, Paucarmayta A, Johnson D, O'Neill T, Cusumano Z, Langermann S, Langenau D, Patel S. The FLRT3-UNC5B Pathway is a Novel Regulator of T Immunosurveillance. The Journal Of Immunology 2024, 212: 0298_5492-0298_5492. DOI: 10.4049/jimmunol.212.supp.0298.5492.Peer-Reviewed Original ResearchT cell activationT cellsCell-derived xenograftsTumor growthT cell anti-tumor immunityInhibitor of T cell activationCell-derived xenograft modelControl T cell responsesHuman T cell functionT cell checkpointsAnti-tumor immunityT cell responsesT cell functionActivated T cellsTumor-immune interactionsPromote tumor growthHuman T cellsCAR-TUNC-5 netrin receptor BZebrafish tumor modelTumor cellsTumor modelReceptor BGain-of-function screenMonoclonal antibodiesTumor expressed BCAM impedes anti-tumor T cell immunity and can be targeted therapeutically
Flies D, Tian L, O'Neill R, Fitzgerald D, Sharee S, Shaik J, Bosiacki J, Paucarmayta A, Prajapati K, Langermann S, Mrass P. Tumor expressed BCAM impedes anti-tumor T cell immunity and can be targeted therapeutically. The Journal Of Immunology 2024, 212: 0517_5466-0517_5466. DOI: 10.4049/jimmunol.212.supp.0517.5466.Peer-Reviewed Original ResearchAnti-tumor immunityT cell immunityCytotoxic T cellsTumor microenvironmentT cellsTumor growthAnti-tumor T cell immunityT cell anti-tumor immunityExclusion of T cellsIncreased T-cell infiltrationRegulating T cell immunityHuman T cell functionT cell infiltrationInhibitor of T cell proliferationT cell suppressionHuman tumors in vitroT cell functionReduced tumor growthT cell proliferationDecreased tumor growthTumors in vitroTumor growth in vivoCancer escapeCheckpoint inhibitorsGrowth in vivoCellular and molecular determinants of limited anti-tumor immunity in chromophobe renal carcinoma (ChRCC).
Labaki C, Alchoueiry M, Bi K, Zhang L, Hobeika C, Bakouny Z, El Ahmar N, Matar S, Priolo C, Khabibullin D, Schindler N, Camp S, Saliby R, Saad E, Signoretti S, Van Allen E, Shukla S, Henske E, Choueiri T, Braun D. Cellular and molecular determinants of limited anti-tumor immunity in chromophobe renal carcinoma (ChRCC). Journal Of Clinical Oncology 2024, 42: 476-476. DOI: 10.1200/jco.2024.42.4_suppl.476.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsAnti-tumor immunityCell of originScRNA-seq dataPutative cell of originHLA class I genesCD8+Class I genesPD-1T cellsI geneSingle-cell T-cell receptorPoor responseResponse to immune checkpoint inhibitorsExpression of HLA class I genesInfiltration of CD8+Infiltration of T cellsCD4+ T cellsDegree of clonal expansionDownregulation of antigen presentationProportion of CD8+T cell clonotypesChromophobe renal carcinomaMolecular determinantsProtein processing pathwayThe CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screensAbstract B117: Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs)
Borazanci E, Pant S, Perets R, Golan T, Al Hallak M, Cecchini M, Maierson T, David H, Schickler M, Reuveni H. Abstract B117: Phase 1 study of CM24 in combination with nivolumab in patients with advanced pancreatic cancer - Survival, potential biomarker and effect on neutrophil extracellular traps (NETs). Cancer Research 2024, 84: b117-b117. DOI: 10.1158/1538-7445.panca2023-b117.Peer-Reviewed Original ResearchPancreatic ductal adenocarcinoma patientsTumor-infiltrating lymphocytesPancreatic ductal adenocarcinomaNeutrophil extracellular trapsCarcinoembryonic antigen cell adhesion molecule 1Dose-escalation partPancreatic cancer survivalImmune evasionExtracellular trapsEscalation partPatient biopsiesPotential biomarkersRandomized phase 2 studyCompared to healthy volunteersControl immune evasionDisease control ratePhase 1/2 studyAnti-tumor immunitySecond-line therapyCancer survivalPhase 2 studyPhase 1 studyCell adhesion molecule 1Adhesion molecule 1Patient survival data
2023
The 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 tumors1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. 1025 Tumor-specific CD8+ T cells epigenetically licensed by IL-7R are critical for anti-tumor immunity in melanoma. 2023, a1133-a1133. DOI: 10.1136/jitc-2023-sitc2023.1025.Peer-Reviewed Original ResearchAssociations amongst genes, molecules, cells, and organs in breast cancer metastasis
Nathanson S, Dieterich L, Zhang X, Chitale D, Pusztai L, Reynaud E, Wu Y, Ríos-Hoyo A. Associations amongst genes, molecules, cells, and organs in breast cancer metastasis. Clinical & Experimental Metastasis 2023, 41: 417-437. PMID: 37688650, DOI: 10.1007/s10585-023-10230-w.Peer-Reviewed Original ResearchBreast cancer metastasisBreast cancerCancer metastasisOutcomes of patientsAnti-tumor immunityHope of cureAggressive therapyMultiple metastasesAggressive treatmentBone metastasesLymph nodesSystemic metastasesMorphologic subtypesClinical oncologistsMetastasisInternal visceraAssists cliniciansLymphatic endothelial cellsPatientsEndothelial cellsHealth SymposiumBasic scientistsMolecular expressionCancerMolecular aspectsEndothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src
Sjöberg E, Melssen M, Richards M, Ding Y, Chanoca C, Chen D, Nwadozi E, Pal S, Love D, Ninchoji T, Shibuya M, Simons M, Dimberg A, Claesson-Welsh L. Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src. Journal Of Clinical Investigation 2023, 133: e161366. PMID: 37651195, PMCID: PMC10575733, DOI: 10.1172/jci161366.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseRenal cell carcinomaAnti-tumor immunityVascular leakageT cellsEndothelial barrierClear cell renal cell carcinomaCell renal cell carcinomaRegulatory T cellsHelper T cellsNitric oxide synthaseImmune cell activationAntitumor immunityImmunosuppressive cytokinesPoor prognosisCell carcinomaPLCγ pathwayOxide synthaseVascular permeabilityB cellsActivation of PLCγCell activationTumor vesselsDecreased expressionCancer forms
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