2025
Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes
Rodriguez-Sevilla J, Ganan-Gomez I, Kumar B, Thongon N, Ma F, Chien K, Kim Y, Yang H, Loghavi S, Tan R, Adema V, Li Z, Tanaka T, Uryu H, Kanagal-Shamanna R, Al-Atrash G, Bejar R, Banerjee P, Lynn Cha S, Montalban-Bravo G, Dougherty M, Fernandez Laurita M, Wheeler N, Jia B, Papapetrou E, Izzo F, Dueñas D, McAllen S, Gu Y, Todisco G, Ficara F, Della Porta M, Jain A, Takahashi K, Clise-Dwyer K, Halene S, Bertilaccio M, Garcia-Manero G, Daher M, Colla S. Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes. Nature Communications 2025, 16: 3450. PMID: 40216768, DOI: 10.1038/s41467-025-58662-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsMyelodysplastic syndromeImmune escapeMyelodysplastic syndrome hematopoietic stem cellsNatural killer (NK) cellsAberrant hematopoietic stem cellsEarly-stage myelodysplastic syndromeDevelopment of myelodysplastic syndromeStage of myelodysplastic syndromeAdoptive cell therapyFunctional in vitro studiesNatural killer cellsTime of diagnosisPreclinical in vivo studiesPre-malignant clonesDisease-related comorbiditiesPre-malignant stageSlow down disease progressionRegenerate hematopoiesisClonal cytopeniaNK cellsImmune surveillanceKiller cellsHealthy donorsPharmacological therapyTrogocytosis-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
Targeting immune evasion in hepatocellular carcinoma-initiating cells
Sirera R, Beltrán-Visiedo M, Galluzzi L. Targeting immune evasion in hepatocellular carcinoma-initiating cells. Trends In Immunology 2024, 46: 4-6. PMID: 39721855, DOI: 10.1016/j.it.2024.12.002.Peer-Reviewed Original Research
2023
A membrane-associated MHC-I inhibitory axis for cancer immune evasion
Chen X, Lu Q, Zhou H, Liu J, Nadorp B, Lasry A, Sun Z, Lai B, Rona G, Zhang J, Cammer M, Wang K, Al-Santli W, Ciantra Z, Guo Q, You J, Sengupta D, Boukhris A, Zhang H, Liu C, Cresswell P, Dahia P, Pagano M, Aifantis I, Wang J. A membrane-associated MHC-I inhibitory axis for cancer immune evasion. Cell 2023, 186: 3903-3920.e21. PMID: 37557169, PMCID: PMC10961051, DOI: 10.1016/j.cell.2023.07.016.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSolid cancersImmune evasionCancer immune evasionImmune checkpoint blockadeMultiple solid cancersMajor Histocompatibility Complex Class I Antigen PresentationPotential therapeutic targetCell-dependent mannerCell immunityCancer survivalMyeloid leukemiaAntigen presentationTherapeutic targetTransmembrane protein 127Tumor growthGene signatureCancer treatmentCancerPeptide-MHCMHCLeukemiaSushi domainTrimolecular complexE3 ubiquitin ligase WWP2
2022
DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion
Chen B, Hu J, Hu X, Chen H, Bao R, Zhou Y, Ye Y, Zhan M, Cai W, Li H, Li HB. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nature Communications 2022, 13: 2059. PMID: 35440133, PMCID: PMC9018773, DOI: 10.1038/s41467-022-29754-y.Peer-Reviewed Original ResearchConceptsPD-L1 expressionTumor immune evasionImmune evasionReduced PD-L1 expressionDeath ligand 1Tumor-killing activityT cellsTherapeutic targetTumor growthCancer cellsCRISPR/Cas9 screeningLigand 1Cell homeostasisKinase 2ExpressionEvasionCD8ImmunotherapyCellsIFNγDysfunctionRBP dysfunctionTumorsCancer
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeSpatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma
Griffin GK, Weirather JL, Roemer MGM, Lipschitz M, Kelley A, Chen PH, Gusenleitner D, Jeter E, Pak C, Gjini E, Chapuy B, Rosenthal MH, Xu J, Chen BJ, Sohani AR, Lovitch SB, Abramson JS, Ishizuka J, Kim AI, Jacobson CA, LaCasce AS, Fletcher CD, Neuberg D, Freeman GJ, Hodi FS, Wright K, Ligon AH, Jacobsen ED, Armand P, Shipp MA, Rodig SJ. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma. Blood 2021, 137: 1353-1364. PMID: 32871584, PMCID: PMC8555417, DOI: 10.1182/blood.2020006464.Peer-Reviewed Original ResearchConceptsT-cell/histiocyte-rich large B-cell lymphomaLarge B-cell lymphomaB-cell lymphomaMalignant B cellsDiffuse large B-cell lymphomaClassic Hodgkin lymphomaPD-1B cellsImmune signaturesImmune escapePD-1/PD-L1 pathwayPD-L1/PDImmune escape pathwayPD-1 blockadeImmune cell infiltratesPD-L1 expressionRefractory hematologic malignanciesPD-L1 pathwayMulti-institutional cohortClinical responsePartial responseCell infiltrateComplete responsePD-L1Aggressive variantAn expanded universe of cancer targets
Hahn W, Bader J, Braun T, Califano A, Clemons P, Druker B, Ewald A, Fu H, Jagu S, Kemp C, Kim W, Kuo C, McManus M, B. Mills G, Mo X, Sahni N, Schreiber S, Talamas J, Tamayo P, Tyner J, Wagner B, Weiss W, Gerhard D, Dancik V, Gill S, Hua B, Sharifnia T, Viswanathan V, Zou Y, Dela Cruz F, Kung A, Stockwell B, Boehm J, Dempster J, Manguso R, Vazquez F, Cooper L, Du Y, Ivanov A, Lonial S, Moreno C, Niu Q, Owonikoko T, Ramalingam S, Reyna M, Zhou W, Grandori C, Shmulevich I, Swisher E, Cai J, Chan I, Dunworth M, Ge Y, Georgess D, Grasset E, Henriet E, Knútsdóttir H, Lerner M, Padmanaban V, Perrone M, Suhail Y, Tsehay Y, Warrier M, Morrow Q, Nechiporuk T, Long N, Saultz J, Kaempf A, Minnier J, Tognon C, Kurtz S, Agarwal A, Brown J, Watanabe-Smith K, Vu T, Jacob T, Yan Y, Robinson B, Lind E, Kosaka Y, Demir E, Estabrook J, Grzadkowski M, Nikolova O, Chen K, Deneen B, Liang H, Bassik M, Bhattacharya A, Brennan K, Curtis C, Gevaert O, Ji H, Karlsson K, Karagyozova K, Lo Y, Liu K, Nakano M, Sathe A, Smith A, Spees K, Wong W, Yuki K, Hangauer M, Kaufman D, Balmain A, Bollam S, Chen W, Fan Q, Kersten K, Krummel M, Li Y, Menard M, Nasholm N, Schmidt C, Serwas N, Yoda H, Ashworth A, Bandyopadhyay S, Bivona T, Eades G, Oberlin S, Tay N, Wang Y, Weissman J. An expanded universe of cancer targets. Cell 2021, 184: 1142-1155. PMID: 33667368, PMCID: PMC8066437, DOI: 10.1016/j.cell.2021.02.020.Peer-Reviewed Original ResearchConceptsNon-oncogene dependenciesDiversity of therapeutic targetsSomatically altered genesCancer targetCancer allelesInfluence therapyCancer genomesGenomic characterizationTherapeutic strategiesAltered genesCancer featuresCancer genesClinical translationCancerCancer biologyTherapeutic targetTumorGenomeGenesAneuploidy as a promoter and suppressor of malignant growth
Vasudevan A, Schukken KM, Sausville EL, Girish V, Adebambo OA, Sheltzer JM. Aneuploidy as a promoter and suppressor of malignant growth. Nature Reviews Cancer 2021, 21: 89-103. PMID: 33432169, DOI: 10.1038/s41568-020-00321-1.Peer-Reviewed Original Research
2020
Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors
Li J, Duran M, Dhanota N, Chatila W, Bettigole S, Kwon J, Sriram R, Humphries M, Salto-Tellez M, James J, Hanna M, Melms J, Vallabhaneni S, Litchfield K, Usaite I, Biswas D, Bareja R, Li H, Martin M, Dorsaint P, Cavallo J, Li P, Pauli C, Gottesdiener L, DiPardo B, Hollmann T, Merghoub T, Wen H, Reis-Filho J, Riaz N, Su S, Kalbasi A, Vasan N, Powell S, Wolchok J, Elemento O, Swanton C, Shoushtari A, Parkes E, Izar B, Bakhoum S. Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors. Cancer Discovery 2020, 11: 1212-1227. PMID: 33372007, PMCID: PMC8102348, DOI: 10.1158/2159-8290.cd-20-0387.Peer-Reviewed Original ResearchConceptsChromosomally unstable tumorsAnti-PD-1/PD-L1 treatmentResponse to immune checkpoint blockadeReduced immune cell infiltrationUnstable tumorsGeneration of extracellular adenosineCancer cells to immune cellsImmune-suppressive pathwaysImmune checkpoint blockadeResistance to immunotherapyTumor immune infiltrationImmune cell infiltrationEvading immune surveillanceMetastatic cancer cellsCGAS-STING innate immune pathwayExtracellular cGAMPCheckpoint blockadeInnate immune pathwaysTumor inflammationImmune surveillanceExtracellular adenosineImmune infiltrationIncreased metastasisImmune cellsCell infiltrationCancer Epigenetics, Tumor Immunity, and Immunotherapy
Cao J, Yan Q. Cancer Epigenetics, Tumor Immunity, and Immunotherapy. Trends In Cancer 2020, 6: 580-592. PMID: 32610068, PMCID: PMC7330177, DOI: 10.1016/j.trecan.2020.02.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune responseAntitumor immune responseCancer-immunity cycleAnticancer immune responseEpigenetic targeting agentsImpaired immunosurveillanceCurrent immunotherapiesTumor immunityImmunomodulatory drugsImmune cellsImmune restrictionTargeting agentEpigenetic mechanismsEpigenetic regulatorsImmunotherapyPharmaceutical modulationEpigenetic therapyTumorsImmunosurveillanceTherapyCurrent advancesDNA methylationImmunityResponseNormalization Cancer Immunotherapy for Melanoma
Vesely MD, Chen L. Normalization Cancer Immunotherapy for Melanoma. Journal Of Investigative Dermatology 2020, 140: 1134-1142. PMID: 32092349, PMCID: PMC7247948, DOI: 10.1016/j.jid.2020.02.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNormalization cancer immunotherapyCancer immunotherapyImmune responseDysfunctional immune responseSystemic immune responsesContext of melanomaPatient survivalTreatment of cancerTumor responseImmunotherapyToxicity profileImmune systemTumor microenvironmentMelanomaCancerDistinct mechanismsResponseCliniciansVaccine and Cell-based Therapeutic Approaches in Acute Myeloid Leukemia
Agrawal V, Gbolahan OB, Stahl M, Zeidan AM, Zaid MA, Farag SS, Konig H. Vaccine and Cell-based Therapeutic Approaches in Acute Myeloid Leukemia. Current Cancer Drug Targets 2020, 20: 473-489. PMID: 32357813, DOI: 10.2174/1568009620666200502011059.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntibodies, MonoclonalAntigens, NeoplasmAntineoplastic Agents, ImmunologicalCancer VaccinesHematopoietic Stem Cell TransplantationHumansImmunotherapy, AdoptiveKiller Cells, NaturalLeukemia, Myeloid, AcuteReceptors, Chimeric AntigenT-Lymphocytes, CytotoxicTransplantation, HomologousTumor EscapeConceptsAcute myeloid leukemiaTumor-associated antigensImmune systemAML cellsMyeloid leukemiaTreatment of AMLAllogeneic stem cell transplantationEffective immunotherapeutic strategiesNatural killer cellsStem cell transplantationHumoral immune reactionsCell-based therapeutic approachesSurface receptor expressionAcute leukemia cellsDirect immunosuppressionImmunotherapeutic strategiesTreatment landscapeImmunotherapeutic approachesCellular immunotherapyKiller cellsCell transplantationClinical managementHematologic malignanciesReceptor expressionDecreased immunogenicity
2019
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
Jansen C, Prokhnevska N, Master V, Sanda M, Carlisle J, Bilen M, Cardenas M, Wilkinson S, Lake R, Sowalsky A, Valanparambil R, Hudson W, McGuire D, Melnick K, Khan A, Kim K, Chang Y, Kim A, Filson C, Alemozaffar M, Osunkoya A, Mullane P, Ellis C, Akondy R, Im S, Kamphorst A, Reyes A, Liu Y, Kissick H. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature 2019, 576: 465-470. PMID: 31827286, PMCID: PMC7108171, DOI: 10.1038/s41586-019-1836-5.Peer-Reviewed Original ResearchConceptsCD8 T cellsStem-like CD8 T cellsT cellsStem-like T cellsCD8 T cell infiltrationCD8 T cell responsesMechanism of immune escapeTumor-infiltrating lymphocytesT cell infiltrationT cell responsesStem-like cellsSurvival benefitImmune nicheProgressive diseaseImmune escapeTumor typesTumorCD8Human cancersDifferentiation processLymphocytesPatientsCancerInfiltrationSurvivalGlutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone R, Zhao L, Englert J, Sun I, Oh M, Sun I, Arwood M, Bettencourt I, Patel C, Wen J, Tam A, Blosser R, Prchalova E, Alt J, Rais R, Slusher B, Powell J. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366: 1013-1021. PMID: 31699883, PMCID: PMC7023461, DOI: 10.1126/science.aav2588.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzo CompoundsCaproatesCD8-Positive T-LymphocytesCitric Acid CycleEnergy MetabolismFemaleGlucoseGlutamineImmunologic MemoryImmunotherapy, AdoptiveLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalTumor EscapeTumor MicroenvironmentConceptsEffector T cellsT cellsTumor immune evasionCancer cellsPotent antitumor responsesImmune cell functionAntitumor responseImmunosuppressive microenvironmentTumor immunotherapyCancer immunotherapyMice suppressesImmune evasionCell functionOxidative metabolismGlycolytic metabolismGlutamine antagonistImmunotherapyMetabolic characteristicsMetabolic programsTumorsMetabolic checkpointDivergent changesMetabolismCellsAntagonism
2018
Oncolytic virus immunotherapy: future prospects for oncology
Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. Journal For ImmunoTherapy Of Cancer 2018, 6: 140. PMID: 30514385, PMCID: PMC6280382, DOI: 10.1186/s40425-018-0458-z.Peer-Reviewed Original ResearchConceptsOncolytic virusesSevere immune-related adverse eventsImmune-related adverse eventsAnti-tumor immune responseEarly-stage clinical trialsImmune checkpoint inhibitorsSerious adverse effectsOncolytic viral therapyLimited therapeutic responseAnti-cancer treatmentLocal target cellsCheckpoint inhibitorsSalvage therapyTolerability profileCytotoxic chemotherapyAdverse eventsImmune dysregulationOncologic careTherapeutic optionsTumor bedSuch therapyTherapeutic responseClinical trialsNovel therapiesViral therapyAcquired mechanisms of immune escape in cancer following immunotherapy
Iorgulescu J, Braun D, Oliveira G, Keskin D, Wu C. Acquired mechanisms of immune escape in cancer following immunotherapy. Genome Medicine 2018, 10: 87. PMID: 30466478, PMCID: PMC6249768, DOI: 10.1186/s13073-018-0598-2.Peer-Reviewed Original ResearchImmunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markersDefining and Understanding Adaptive Resistance in Cancer Immunotherapy
Kim TK, Herbst RS, Chen L. Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends In Immunology 2018, 39: 624-631. PMID: 29802087, PMCID: PMC6066429, DOI: 10.1016/j.it.2018.05.001.Peer-Reviewed Original ResearchConceptsAnti-PD therapyLong-term survival benefitAvailable treatment regimensFraction of respondersSurvival benefitTumor immunityTumor-immune interactionsAdvanced cancerTreatment regimensCancer immunotherapyTumor regressionTherapyAccurate tissueSuch treatmentAdaptive resistancePatientsMolecular mechanismsTrue resistanceImmunotherapyRegimensRight targetCancerRespondersImmunityAppropriate interpretationDKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation
Xiao Q, Wu J, Wang WJ, Chen S, Zheng Y, Yu X, Meeth K, Sahraei M, Bothwell ALM, Chen L, Bosenberg M, Chen J, Sexl V, Sun L, Li L, Tang W, Wu D. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nature Medicine 2018, 24: 262-270. PMID: 29431745, PMCID: PMC5840007, DOI: 10.1038/nm.4496.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli Proteinbeta CateninCD8-Positive T-LymphocytesCell Line, TumorColorectal NeoplasmsCytotoxicity, ImmunologicGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsIntestinal NeoplasmsKiller Cells, NaturalLow Density Lipoprotein Receptor-Related Protein-5MelanomaProgrammed Cell Death 1 ReceptorPTEN PhosphohydrolaseSignal TransductionSTAT5 Transcription FactorTumor Escape
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