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
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 presentationTherapeutic 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 damageNanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy
Wang-Bishop L, Wehbe M, Pastora L, Yang J, Kimmel B, Garland K, Becker K, Carson C, Roth E, Gibson-Corley K, Ulkoski D, Krishnamurthy V, Fedorova O, Richmond A, Pyle A, Wilson J. Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy. ACS Nano 2024, 18: 11631-11643. PMID: 38652829, PMCID: PMC11080455, DOI: 10.1021/acsnano.3c06225.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsTumor microenvironmentLipid nanoparticlesBreast cancerResponse to ICIResponse to immune checkpoint inhibitorsInfiltration of CD8<sup>+</sup>Models of triple-negative breast cancerCD4<sup>+</sup> T cellsInhibition of tumor growthTriple-negative breast cancerRIG-IIonizable lipid nanoparticlesLung metastatic burdenIncrease tumor immunogenicityBreast tumor microenvironmentSignaling in vitroACTLA-4Immunogenic melanomaCheckpoint inhibitorsTumor immunogenicityImmunotherapeutic modalitiesCancer immunotherapyMetastatic burdenAPD-1
2022
Cancer 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 subspecialtyImmunogenicityMicroenvironmentPatientsLCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer
Pérez-Núñez I, Rozalén C, Palomeque JÁ, Sangrador I, Dalmau M, Comerma L, Hernández-Prat A, Casadevall D, Menendez S, Liu DD, Shen M, Berenguer J, Ruiz IR, Peña R, Montañés JC, Albà MM, Bonnin S, Ponomarenko J, Gomis RR, Cejalvo JM, Servitja S, Marzese DM, Morey L, Voorwerk L, Arribas J, Bermejo B, Kok M, Pusztai L, Kang Y, Albanell J, Celià-Terrassa T. LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer. Nature Cancer 2022, 3: 355-370. PMID: 35301507, DOI: 10.1038/s43018-022-00339-4.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCancer stem cellsLigand-dependent corepressorTumor immunogenicityBreast cancerImmune checkpoint blockadeBreast cancer metastasisICB efficacyICB resistanceLCoR expressionClinical responsePresentation machineryImmune escapeAPM genesPreclinical modelsTherapy resistanceCancer metastasisPromising targetOvercame resistanceIFNRNA therapyCancerImmunogenicitySignaling-independent mannerStem cellsImmune checkpoint inhibitors for recurrent endometrial cancer
Mutlu L, Harold J, Tymon-Rosario J, Santin AD. Immune checkpoint inhibitors for recurrent endometrial cancer. Expert Review Of Anticancer Therapy 2022, 22: 249-258. PMID: 35176955, DOI: 10.1080/14737140.2022.2044311.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRecurrent endometrial cancerCheckpoint inhibitorsEndometrial cancerEC patientsAdvanced/recurrent endometrial cancerPD-1/PD-L1 inhibitorsRecurrent EC patientsUse of chemotherapyCommon gynecologic malignancyMajor clinical trialsPD-L1 inhibitorsBiomarkers of responseViable treatment optionHuman cancer treatmentTumor microenvironment immunosuppressionRecurrent diseaseGynecologic malignanciesPD-1Clinical efficacyPatient populationTreatment optionsTumor immunogenicityRecent trialsClinical trials
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 therapyBlockade
2020
CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade
Wang G, Chow RD, Zhu L, Bai Z, Ye L, Zhang F, Renauer PA, Dong MB, Dai X, Zhang X, Du Y, Cheng Y, Niu L, Chu Z, Kim K, Liao C, Clark P, Errami Y, Chen S. CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade. Cancer Discovery 2020, 10: 1912-1933. PMID: 32887696, PMCID: PMC7710536, DOI: 10.1158/2159-8290.cd-19-1448.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCheckpoint blockadeCancer typesMajority of patientsRemarkable clinical efficacyFraction of patientsMajor modulatorComplex molecular landscapeMultiple cancer typesClinical efficacyICB responseImmune infiltrationTumor immunogenicityAntigen presentationMutation burdenMouse modelPatient stratificationMutant tumorsTumor microenvironmentIssue featurePatientsTumorsMolecular landscapeBlockadeCancerOptimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists
Ho AY, Wright JL, Blitzblau RC, Mutter RW, Duda D, Norton L, Bardia A, Spring L, Isakoff SJ, Chen JH, Grassberger C, Bellon JR, Beriwal S, Khan AJ, Speers C, Dunn SA, Thompson A, Santa-Maria CA, Krop IE, Mittendorf E, King TA, Gupta GP. Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists. International Journal Of Radiation Oncology • Biology • Physics 2020, 108: 227-241. PMID: 32417409, PMCID: PMC7646202, DOI: 10.1016/j.ijrobp.2020.05.011.Peer-Reviewed Original ResearchConceptsBreast cancerRadiation therapyTiming of RTImmune checkpoint blockadeSystemic immune responsesEffector immune cellsSystemic antitumor effectsBreast radiation oncologistsTypes of cancerCheckpoint blockadeTumor immunogenicityImmune cellsClinical trialsImmune responseSystemic effectsAntitumor effectsTranslational studiesHigh dosesRadiation oncologistsImmunotherapyCancerDistant sitesTherapyFurther explorationOncologists
2019
Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumors
2012
Opposing Roles for IL-23 and IL-12 in Maintaining Occult Cancer in an Equilibrium State
Teng MW, Vesely MD, Duret H, McLaughlin N, Towne JE, Schreiber RD, Smyth MJ. Opposing Roles for IL-23 and IL-12 in Maintaining Occult Cancer in an Equilibrium State. Cancer Research 2012, 72: 3987-3996. PMID: 22869585, PMCID: PMC4384890, DOI: 10.1158/0008-5472.can-12-1337.Peer-Reviewed Original ResearchConceptsIL-12IL-23Antibody treatmentImmune systemCD40 antibody treatmentIL‐12/23p40 antibodiesAutoimmune inflammatory disorderMonoclonal antibody treatmentOccult neoplasiaOccult cancerIL-17IL-23p19IL-12/23p40Immune controlInflammatory disordersTumor immunogenicityIL-4Malignant potentialCancer immunoeditingTumor outgrowthElimination phaseTumor growthTumor dormancyMutant cancersCancer cells
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