2024
Mechanisms of immunotherapy resistance in small cell lung cancer
Nie Y, Schalper K, Chiang A. Mechanisms of immunotherapy resistance in small cell lung cancer. Cancer Drug Resistance 2024, 7: n/a-n/a. PMID: 39802951, PMCID: PMC11724353, DOI: 10.20517/cdr.2024.154.Peer-Reviewed Original ResearchSmall-cell lung cancerImmune checkpoint inhibitorsSociety for Immunotherapy of CancerImmunotherapy resistanceTumor microenvironmentPrimary resistanceAcquired resistancePrimary resistance to immune checkpoint inhibitorsLung cancerResistance to immune checkpoint inhibitorsMechanisms of immunotherapy resistanceSmall cell lung cancerImmunosuppressive immune cellsImmunotherapy to chemotherapyResistance to immunotherapySociety for ImmunotherapyImmunotherapy of cancerAggressive neuroendocrine tumorCell lung cancerCheckpoint inhibitorsTumor immunogenicityEffective immunotherapyNeuroendocrine tumorsPoor prognosisAntigen presentationFOS+ B cells: Key mediators of immunotherapy resistance in diverse cancer types
Zhang X, Ma J, Chen Y, Deng X, Zhang Y, Han Y, Tan J, Deng G, Ouyang Y, Zhou Y, Cai C, Zeng S, Shen H. FOS+ B cells: Key mediators of immunotherapy resistance in diverse cancer types. Molecular Therapy Oncology 2024, 32: 200895. PMID: 39583007, PMCID: PMC11584611, DOI: 10.1016/j.omton.2024.200895.Peer-Reviewed Original ResearchImmunotherapy resistanceB cellsPoor response to immunotherapyExpression of Blimp-1Cancer typesResponse to immunotherapyDifferentiation of B cellsB cell subpopulationsAssociated with poor response to immunotherapyPredicting treatment responseAffecting treatment efficacyDiverse cancer typesImmunotherapy efficacyImmunotherapy patientsTumor microenvironmentTreatment responsePlasma cellsImmunotherapyImmunosuppressive effectsBlimp-1Spatial transcriptomic analysisTreatment efficacyOvercome resistanceCancer treatmentImmunofluorescence analysisHLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases.
Vilariño N, Lopez De Rodas M, Ranjan K, Costantini A, Villalba M, Lu B, Kravitz C, Nadal E, Goldberg S, Nguyen D, Schalper K. HLA class-I antigen presentation machinery (APM) alterations mediate immune evasion in lung cancer brain metastases. Journal Of Clinical Oncology 2024, 42: e14014-e14014. DOI: 10.1200/jco.2024.42.16_suppl.e14014.Peer-Reviewed Original ResearchLung cancer brain metastasisPrimary lung tumorsTumor-infiltrating lymphocytesImmune checkpoint inhibitorsCancer brain metastasesAntigen presentation machineryB2M expressionIFN-gBrain metastasesB2MImmune evasionAssociated with shorter overall survivalMultiplexed quantitative immunofluorescenceM expressionExpression of B2MB2M levelsExpression of pSTAT1Shorter overall survivalUnfavorable clinical featuresNo significant associationAssociated with unfavorable clinical featuresCheckpoint inhibitorsImmunotherapy resistanceProperties of tumorsPresentation machineryUnderstanding and overcoming resistance to immunotherapy in genitourinary cancers
Evans S, Jani Y, Jansen C, Yildirim A, Kalemoglu E, Bilen M. Understanding and overcoming resistance to immunotherapy in genitourinary cancers. Cancer Biology & Therapy 2024, 25: 2342599. PMID: 38629578, PMCID: PMC11028033, DOI: 10.1080/15384047.2024.2342599.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsResistance to immunotherapyImmunotherapy resistanceTargeted therapyGenitourinary (GU) cancersCombined immune checkpoint inhibitorsIntroduction of novel immunotherapiesMechanisms of immunotherapy resistanceOvercome resistance to immunotherapyCancer cellsHost immune profileResponse to immunotherapyNovel targeted therapiesImmune system's rolePredictors of responseAttack cancer cellsImmune system's abilityStandard of careCheckpoint inhibitorsSequential therapyNovel immunotherapiesCombination therapyTreatment failureGU cancersTreatment landscape
2023
PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.
Exposito F, Redrado M, Houry M, Hastings K, Molero-Abraham M, Lozano T, Solorzano J, Sanz-Ortega J, Adradas V, Amat R, Redin E, Leon S, Legarra N, Garcia J, Serrano D, Valencia K, Robles-Oteiza C, Foggetti G, Otegui N, Felip E, Lasarte J, Paz-Ares L, Zugazagoitia J, Politi K, Montuenga L, Calvo A. PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells. Cancer Research 2023, 83: 2513-2526. PMID: 37311042, DOI: 10.1158/0008-5472.can-22-3023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLung squamous carcinomaAnti-PD-1 therapyRegulatory T cellsCell lung cancerImmunosuppressive microenvironmentLung cancerImmunotherapy resistanceT cellsWorse progression-free survivalCell death protein 1PTEN lossAnti-TGFβ antibodyConversion of CD4PI3K/AKT/mTOR pathwayProgression-free survivalDeath protein 1Treatment of miceImmunosuppressive tumor microenvironmentPTEN/PI3K/AKT/mTOR pathwayAKT/mTOR pathwayPD-L1TLR agonistsTumor rejectionSquamous carcinomaDeep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer
Barrera C, Corredor G, Viswanathan V, Ding R, Toro P, Fu P, Buzzy C, Lu C, Velu P, Zens P, Berezowska S, Belete M, Balli D, Chang H, Baxi V, Syrigos K, Rimm D, Velcheti V, Schalper K, Romero E, Madabhushi A. Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer. Npj Precision Oncology 2023, 7: 52. PMID: 37264091, PMCID: PMC10235089, DOI: 10.1038/s41698-023-00403-x.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-infiltrating lymphocytesLung cancerEffective adaptive immune responseImmune checkpoint blockersCell lung cancerLung cancer patientsTumor immune microenvironmentAdaptive immune responsesImmune-related biomarkersTreatment-specific outcomesCheckMate 057Histology variantsImmunotherapy resistanceCheckpoint blockersRegulatory cellsTumor rejectionTumor-immune interactionsClinical outcomesImmunosuppressive signalsClinical benefitInfluence prognosisImmune microenvironmentCancer patientsPatient outcomes
2022
148 TAP2 deficiency mediates adaptive immune evasion and immunotherapy resistance in human non-small cell lung cancer
Ranjan K, Deen I, Rodas M, Gianino N, Ferrone S, Schalper K. 148 TAP2 deficiency mediates adaptive immune evasion and immunotherapy resistance in human non-small cell lung cancer. 2022, a161-a161. DOI: 10.1136/jitc-2022-sitc2022.0148.Peer-Reviewed Original Research133 Spatially defined gene signatures uncover the association of extracellular matrix genes with immunotherapy resistance in head and neck squamous cell carcinoma
Gavrielatou N, Warrell J, Aung T, Vathiotis L, Economopoulou P, Burtness B, Psyrri A, Rimm D. 133 Spatially defined gene signatures uncover the association of extracellular matrix genes with immunotherapy resistance in head and neck squamous cell carcinoma. 2022, a146-a146. DOI: 10.1136/jitc-2022-sitc2022.0133.Peer-Reviewed Original ResearchCancer Immunoediting in the Era of Immuno-oncology.
Gubin MM, Vesely MD. Cancer Immunoediting in the Era of Immuno-oncology. Clinical Cancer Research 2022, 28: 3917-3928. PMID: 35594163, PMCID: PMC9481657, DOI: 10.1158/1078-0432.ccr-21-1804.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCancer immunoeditingImmune-tumor cell interactionsCancer immunotherapyAbsence of immunotherapyDurable clinical responsesT cell biologyCell interactionsImmunotherapy resistanceClinical responseImmunosuppressive microenvironmentTumor immunogenicityImmuno-oncologyClinical dataPreclinical modelsImmunoeditingImmunotherapyHuman patientsImmune systemTumor microenvironmentCancerCancer progressionClinical subspecialtyImmunogenicityMicroenvironmentPatientsRefining colorectal cancer classification and clinical stratification through a single-cell atlas
Khaliq A, Erdogan C, Kurt Z, Turgut S, Grunvald M, Rand T, Khare S, Borgia J, Hayden D, Pappas S, Govekar H, Kam A, Reiser J, Turaga K, Radovich M, Zang Y, Qiu Y, Liu Y, Fishel M, Turk A, Gupta V, Al-Sabti R, Subramanian J, Kuzel T, Sadanandam A, Waldron L, Hussain A, Saleem M, El-Rayes B, Salahudeen A, Masood A. Refining colorectal cancer classification and clinical stratification through a single-cell atlas. Genome Biology 2022, 23: 113. PMID: 35538548, PMCID: PMC9092724, DOI: 10.1186/s13059-022-02677-z.Peer-Reviewed Original ResearchConceptsConsensus molecular subtypesTumor microenvironmentAssociated with immunotherapy resistanceCAF subtypesImmune checkpoint inhibitorsHuman CRC samplesIndependent external cohortMechanism of tumorsMSI-HContribution to pathogenesisResultsTumor cellsCheckpoint inhibitorsImmunotherapy resistanceImmunotherapy responseEpithelial levelClinicopathological characteristicsMolecular subtypesClinical stratificationCRC patientsMicroenvironmental cellsPatient prognosisPoor outcomeMSI-H CRCsBackgroundColorectal cancerColorectal cancer classification
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 therapyBlockadeEpigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletionA Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer
2018
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade
Ishizuka JJ, Manguso RT, Cheruiyot CK, Bi K, Panda A, Iracheta-Vellve A, Miller BC, Du PP, Yates KB, Dubrot J, Buchumenski I, Comstock DE, Brown FD, Ayer A, Kohnle IC, Pope HW, Zimmer MD, Sen DR, Lane-Reticker SK, Robitschek EJ, Griffin GK, Collins NB, Long AH, Doench JG, Kozono D, Levanon EY, Haining WN. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 2018, 565: 43-48. PMID: 30559380, PMCID: PMC7241251, DOI: 10.1038/s41586-018-0768-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DeaminaseAnimalsCell Cycle CheckpointsCell Line, TumorCRISPR-Cas SystemsDrug Resistance, NeoplasmFemaleHistocompatibility Antigens Class IImmunotherapyInflammationInterferon-Induced Helicase, IFIH1InterferonsMelanoma, ExperimentalMiceMice, Inbred C57BLPhenotypeProgrammed Cell Death 1 ReceptorReceptors, G-Protein-CoupledRNA EditingRNA-Binding ProteinsRNA, Double-StrandedConceptsImmune checkpoint blockadeCheckpoint blockadeAntigen presentationEffective anti-tumor immunityPD-1 checkpoint blockadeTumor cellsAnti-tumor immunityT cell recognitionSufficient inflammationImmunotherapy resistanceInhibitory checkpointsMost patientsInnate ligandsLoss of functionBlockadeTherapeutic requirementsLoss of ADAR1TumorsCancer cellsCell recognitionInflammationGrowth inhibitionADAR1PresentationCells
2014
Mechanisms of immunotherapy resistance in mCRPC: identifying the enemy on the visceral metastatic battlefield.
Kim JW, Bilusic M, Plimack ER. Mechanisms of immunotherapy resistance in mCRPC: identifying the enemy on the visceral metastatic battlefield. Oncology 2014, 28: 986-90. PMID: 25403631.Peer-Reviewed Original Research
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